capit. plant cell wall deconstruction

MI67CH23-Glass ARI 6 August 2013 11:59

Plant Cell Wall Deconstructionby Ascomycete FungiN. Louise Glass,1 Monika Schmoll,4

Jamie H.D. Cate,2,3 and Samuel Coradetti11Plant and Microbial Biology Department, 2Molecular and Cellular Biology Department,and 3Chemistry Department, University of California, Berkeley, California 94720;email: [email protected] Institute of Technology GmbH (AIT), Health and Environment, Bioresources,3430 Tulln, Austria

Annu. Rev. Microbiol. 2013. 67:47798

First published online as a Review in Advance onJune 28, 2013

The Annual Review of Microbiology is online atmicro.annualreviews.org

This articles doi:10.1146/annurev-micro-092611-150044

Copyright c 2013 by Annual Reviews.All rights reserved

Keywords

Neurospora, Trichoderma, plant cell wall, cellulase, hemicellulase,polysaccharide monooxygenase

Abstract

Plant biomass degradation by fungi requires a diverse set of secreted enzymesand signicantly contributes to the global carbon cycle. Recent advances ingenomic and systems-level studies have begun to reveal how lamentousascomycete species exploit carbon sources in different habitats. These stud-ies have laid the groundwork for unraveling new enzymatic strategies fordeconstructing the plant cell wall, including the discovery of polysaccha-ride monooxygenases that enhance the activity of cellulases. The identi-cation of genes encoding proteins lacking functional annotation, but thatare coregulated with cellulolytic genes, suggests functions associated withplant biomass degradation remain to be elucidated. Recent research showsthat signaling cascades mediating cellulolytic responses often act in a light-dependentmanner and show crosstalk with othermetabolic pathways. In thisreview, we cover plant biomass degradation, from sensing, to transmissionand modulation of signals, to activation of transcription factors and geneinduction, to enzyme complement and function.

477

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Contents

INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478CELL WALL DECONSTRUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479

Cellulose Deconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479Hemicellulose Deconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479Pectin Deconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483

REGULATORY MECHANISMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483Carbon Catabolite Repression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483Chromatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484Transcription Factors Involved in Cellulose Deconstruction . . . . . . . . . . . . . . . . . . . . . . 484Transcription Factors Involved in Hemicellulose and Pectin Deconstruction . . . . . . 485Antisense Transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487Crosstalk Between Regulatory Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487

ENVIRONMENTAL AND DEVELOPMENTAL REGULATIONOF PLANT CELL WALLDEGRADING CAPACITY . . . . . . . . . . . . . . . . . . . . . . . . 487Light . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487Heterotrimeric G-Protein Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489cAMP Pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489pH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490

CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 490

INTRODUCTION

Lignocellulosic plant matter is the most abundant natural material present on earth and is com-posed of four major polymeric building blocks: the polyphenol lignin and three polysaccharides,cellulose, hemicellulose, and pectin. In combinationwith plant cell wallassociated enzymes, struc-tural proteins, and proteoglycans, these components form an intricately linked network that pro-vides strength and durability to the plant cell wall (95).

Photosynthesis converts approximately 100 billion metric tons of CO2 and H2O to celluloseevery year (42), which is exploited industrially as a source of fermentable sugars for the productionof liquid biofuels (22, 90, 139). However, the inability to efciently convert insoluble polysaccha-rides, such as cellulose, to fermentable sugars poses a barrier to commercial production of biofuels(57). Filamentous fungi are among the most efcient degraders of plant biomass and are the mainsource of commercial enzymes used to degrade lignocellulose (64). The most commonly usedorganism for commercial production of cellulases is Trichoderma reesei (Hypocrea jecorina). How-ever, recent work in the model lamentous fungus Neurospora crassa has shown that the varietyof molecular, genetic, and biochemical techniques available for this organism (37) can expediteanalyses of fungal deconstruction of plant biomass.

In this review, we cover environmental and regulatory aspects of production of plant cellwalldegrading enzymes by lamentous fungi, including recent characterization of proteins withnew enzymatic functions associated with cell wall deconstruction. This review focuses on recentdevelopments in studies of lamentous ascomycete fungi, in particular T. reesei, Aspergillus niger,and N. crassa, and concentrates on cellulose, hemicellulose, and pectin deconstruction by theseorganisms.

478 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


CELL WALL DECONSTRUCTION

Cellulose Deconstruction

Cellulose is the most challenging material within plant cell walls to deconstruct. It is composedof glucan chains with repeating (14) D-glucose units that form microbrils in lignocellulosewithin the plant cell wall. The classical scheme for fungal cellulose degradation includes (a)endo-1,4--glucanases [glycoside hydrolase 5 (GH5) family (21)] that cleave internal bonds inthe cellulose chain; (b) exo-1,4--glucanases or cellobiohydrolases (GH7 and GH6) that cleavecellobiose molecules from either the reducing or nonreducing ends of a cellulose chain; and(c) -glucosidases (GH3) that hydrolyze cellobiose into two glucose molecules (133) (Figure 1).InT. reesei, Cel7A/CBH1 and Cel6A/CBH2 account for 80% of the total secreted protein undercellulose-inducing conditions; Cel7A alone represents 60% of this amount (87). In N. crassa, 65%of the secretome is made up of four proteins (CBH-1, GH6-2, GH5-1, and GH3-4) (94). Synergybetween exoglucanases (Cel7A) and endoglucanases (Cel5A) has been observed during hydrolysisof bacterial cellulose (61). Similarly, although application of puried Cel7A or Cel6A to cellulosemicrobrils showed halting (so-called trafc jams) (59), ammonia-treated cellulose was completelydegraded by the synergistic action of these two enzymes.

After GH5-1, CBH-1, GH6-2, and GH3-4, the next most abundant group of proteins in theN. crassa cellulose secretome includes three GH61 proteins (94). Previously, GH61 proteins wereclassied as endoglucanases (62). However, recent work in N. crassa and in Thermoascus auranti-acus showed that GH61 proteins encode a novel class of copper-dependent enzymes, now calledpolysaccharide monooxygenases (PMOs), that catalyze the oxidative cleavage of cellulose in thepresence of an external electron donor (12, 98). Although the specic catalytic mechanism is thesubject of current research (58), in nature GH61 enzymes likely receive electrons from the actionof cellobiose dehydrogenases (93, 125) (Figure 2). In N. crassa, deletion of a single cellobiosedehydrogenase gene reduced the total cellulase activity secreted by the fungus by nearly half,indicating that a redox-active system is a signicant part of the cellulolytic machinery (93).

The number of genes encoding members of the GH61 family is quite variable among la-mentous fungi. For example, members of the Sordariomycetes, such as Chaetomium globosum (Cg),Myceliophthora thermophila (Mt), Thielavia terrestris (Tt), and N. crassa (Nc), have a highly expandedPMO (GH61) family, whereas this family is reduced in T. reesei (Tr) and Aspergillus niger (An) (14,53) (Figure 3). However, a comparative analysis of RNA-Seq data shows that the levels of expres-sion of GH61 genes do not simply correlate with the number present in the genome (Figure 3).The relative induction of some GH61 genes on plant biomass can also vary depending on the spe-cic feedstock (14). Because lamentous ascomycete genomes encode and express multiple PMOvariants, these enzymes may have specic targets in the plant cell wall ultrastructure (Figure 2b).

The secretomes of lamentous ascomycete species when exposed to cellulose remain to befully characterized. For example, proteins similar to plant cell wall expansins, termed swollenins,have been identied (102). Swollenins contain a carbohydrate binding domain (CBM) and havebeen proposed to disrupt cellulose structure via nonhydrolytic mechanisms (25, 102, 138), al-though the biochemical action of these proteins remains to be fully elucidated (60, 136). Recently,CBM33-containing proteins have also been implicated in cellulose deconstruction (58). As sub-strate accessibility is one key issue in plant cell wall degradation, accessory proteins are likely toenhance the efciency of this process (40).

Hemicellulose Deconstruction

Hemicellulose is a group of heterogeneous polysaccharides, a major fraction of which arerepresented by xylans substituted with arabinose, glucuronic acid, or other hexose sugars (11).

www.annualreviews.org Plant Cell Wall Deconstruction 479

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Cellobiohydrolase I (GH7)Cellulose

Cellobiohydrolase II (GH6)Endoglucanase (GH5.5)

Polysaccharide monooxygenase (PMO/GH61)

Cellobiose dehydrogenase (CDH)

e

XylanAcetylxylan esterase (CE1CE7)

-Glucuronidase (GH67)

Endo--1,4-xylanase (GH10, GH11)

-L-Arabinofuranosidase(GH3, GH10, GH43, GH51, GH54, GH62)

Feruloyl esterase (CE1)

Lignin

Xyloglucan Galactomannan

-Galactosidase(GH1, GH2, GH3,

GH35, GH42)

-L-Arabinofuranosidase

Xyloglucanase (GH44, GH74)

-Fucosidase(GH1, GH29, GH30, GH95)-Xylosidase

(GH31)-Galactosidase

(GH27, GH36)

Endo--1,4-mannase (GH5.7)

D-glucoseD-galactoseD-mannose

D-glucuronic acidD-galacturonic acidD-arabinofuranose

Feruloyl groupO-acetylO-methyl

Enzyme activity

D-xyloseL-rhamnoseL-fucose

Feruloyl esterase -Glucuronidase(GH1, GH2, GH79)

-L-Arabinofuranosidase

Arabinanase (GH43, GH93)

Endo--1,4-galactanase (GH35, GH53)

Endo--1,6-galactanase (GH5, GH30)

-galactosidase

Exopolygalacturonase

Endopolygalacturonase (GH28)

Rhamnogalacturonan-acetylesterase (CE12)

Rhamnogalacturonan lyase (PL4, PL11)

Pectin methylesterase (CE8, CE12)

Pectin acetylesterase (CE12)

Endoxylogalacturonan hydrolase (GH28)

Rhamnogalacturonase (GH28)

Pectate lyase (PL1)

Homogalacturonan Rhamnogalacturonan I

480 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


OH

OH

OHHO

HOHORO ORO

O OH H1 4

O

OH

OH

OHHO

HOHORO ORO

HO OH

O

OH

OH

OHHO

HOHORO ORO

OH OH

O2+2e+2H+ H2O

H2O

PMO/CDH

a

b

10.5

10.6

10.410.4

16.5

15.5

8.2

8.3

8.3

CBM1 TtGH61E TaGH61A NcPMO-3

Figure 2Oxidation of glucan chains in cellulose by polysaccharide monooxygenase (PMO) enzymes. (a) Oxidationchemistry catalyzed by the combined activity of cellobiose dehydrogenase (CDH) and PMOs, generatingcleaved glucan chains. (b) Proposed targeting of PMOs to the hydrophobic face of cellulose 1 by utilizingat binding surfaces and aromatic residues, analogous to carbohydrate binding domain 1 (CBM1) (63). Theposition of the N-terminal histidine in the PMO active site is also shown for Thielavia terrestris GH61(TtGH61E) (55), as well as N-3-methylation for Thermoascus aurantiacus GH61 (TaGH61A) (98) andNeurospora crassa PMO-3 (NcPMO-3) (69). The active site copper for NcPMO-3 is shown for reference.The glucan chains are shown as black lines, with distances in angstroms between pyranose units labeled withred dotted lines. Distances between aromatic residues in angstroms are labeled with blue dotted lines.Alternative binding of each protein can be formed by moving along the glucan chain by an odd number ofpyranose units, as illustrated for two PMO-3 enzymes to the right. Figure adapted from Reference 69.

Hemicellulose provides extensive cross-linking between cellulose microbrils (117) and isthe second most abundant component of the plant cell wall (117). A variety of enzymes arerequired for xylan degradation (34) (Figure 1), including endo--1,4 xylanases (GH10, GH11),-L-arabinofuranosidases (GH3, GH10, GH43, GH51, GH54, and GH62), -xylosidases(GH43 and GH3), acetylxylan esterases (CE1CE7), and ferulic acid esterases (CE1). As withgenes encoding cellulose-degrading enzymes, the number of predicted hemicellulase genes variesamong lamentous ascomycete fungi (Figure 3). For example, T. reesei shows a reduction in genesencoding GH43 enzymes, but an increase in genes encoding -glucuronidases (GH79) (53).

In A. niger and T. reesei, exposure to xylose induces hemicellulase genes, as well as enzymesinvolved in xylose utilization (xylose reductase and D-xylulokinase), although levels above 1 mM

Figure 1Activities of major Carbohydrate Active enZyme (CAZy) (21) classes on common glycoside linkages in the plant cell wallpolysaccharides cellulose, hemicellulose (xylan, xyloglucan, galactomannan), and pectin (homogalacturonan andrhamnogalacturonan I). Note that many CAZy classes show a broad range of activities (133). The most well-characterized enzymaticactivities are summarized here.


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


o

0 0

50

100

150

200

Gen

es

150

100

50

x1,000 FPKM

G BCg

G BMt

G BTt

G ANc

G WAn

GTr

*

**

* **

**

+

++

+

+++

+

+

+

+

o

o

+

*

o

o

o

o

o

o

o

o

o

CE12CE8PLPL4PL3PL1GH93GH105GH88GH78GH28GH36GH35GH27GH131GH5GH62GH51GH43GH2CE5CE4CE3 CE1GH11GH10GH5-7GH74GH12GH3GH1GH5-5GH6GH7GH61CDH

CAZy gene count and expression data

Figure 3Genome Carbohydrate Active enZymes (CAZy) and expression data from lamentous ascomycete fungi.Predictions are given for Aspergillus niger (An) CBS 513.88 (5), Trichoderma reesei (Tr) (80), Chaetomiumglobosum (Cg) CBS 148.51 (17), Thielavia terrestris (Tt) NRRL 8126, Myceliophthora thermophila (Mt) ATCC42464 (14), and Neurospora crassa (Nc) OR74A (46). Enzyme class predictions shown are from the CAZy (21)database except for T. reesei (53) and C. globosum (97). Classes are grouped according to their activities onmajor components of plant cell walls, although many classes include a broad range of activities that may acton many polymers. Total transcript abundance is shown for major CAZy classes from published fungalRNA-Seq data: N. crassa (27), A. niger (31), M. thermophila, C. globosum, and T. terrestris (14). Libraries werereprocessed from the raw sequence data with current genomic annotations and identical software andsettings where possible. Processing of A. niger libraries required some customization as they were performedon the ABI SOLiD sequencing platform, whereas the others were all performed on Illumina platforms.FPKM (fragments per kilobase of transcript per million mapped reads) values as calculated by Cufinks wereaveraged from among biological replicates and pooled for all enzymes of each class. CAZy classes GH7,GH28, and GH61 are highlighted with symbols +, o, and , respectively. Abbreviations: B, bagasse; A,Avicel; W, wheat straw.

482 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


have the opposite effect (4, 30, 75). In T. reesei, L-arabitol, a metabolite in the degradation cas-cade of L-arabinose, can also induce xylanase expression (74, 75). In contrast to A. niger andT. reesei, most genes encoding hemicellulases are not induced when N. crassa is exposed to xylose(124), but exposure to xylan induces350 genes, includingmany predicted hemicellulase enzymesdescribed above, as well as genes encoding proteins of unknown biochemical function (i.e., hy-pothetical proteins) (124). Strains containing deletions of genes encoding proteins identied inthe secretome, including hemicellulases and hypothetical proteins, show altered protein secretionlevels and enzymatic activities and are ripe for future study.

Pectin Deconstruction

Among plant cell wall polysaccharides, pectin has the highest structural and functional complex-ity (54, 82), with four major structural classes: homogalacturonan (HG), rhamnogalacturonan I(RG-I), xylogalacturonan (XG), and rhamnogalacturonan II (RG-II) (Figure 1). HG is composedof -1,4-linked D-galacturonic acid (D-Gal) residues and accounts for 60% of the pectin in plantcell walls (19). RG-I is the second most abundant pectin class and is composed of a unique back-bone of repeating units of [D-GalA-1,2--L-Rha-1,4]n, which can be substituted at the C-4position with either arabinan, galactan, or arabinogalactan side chains.

A number of enzymes are necessary for efcient degradation of pectin (78), including polygalac-turonases and rhamnogalacturonases (GH28), polysaccharide lyases (pectin and pectate lyases,PL1, PL2, and PL3), and rhamnogalacturonan lyases (PL4), as well as pectin methylesterases(CE8), pectin acetylesterases (CE12 and CE13), and rhamnogalacturonan acetylesterases (CE12).Enzymes that function on RG-I side chain substitutions include arabinanases (GH43, GH93),arabinosidases/-arabinofuranosidases (GH3, GH43, GH51, GH54, and GH62), galactanases(GH5, GH16, GH30, GH35, and GH53), - and -galactosidases (GH1, GH2, GH4, GH16,GH27, GH35, GH36, GH42, GH43, and GH53), -glucuronidases (GH1, GH2, and GH79),and feruloyl esterases (CE1).

Of the 60 genes identied in the A. niger genome predicted to encode pectinolytic enzymes,the expression of 46 was detected (78); a large number of these pectin-degrading enzymes havebeen identied experimentally by mass spectrometry (131). Similar to predicted cellulase andhemicellulase genes, the number of genes encoding pectin-degrading enzymes is also variable inlamentous ascomycete genomes (Figure 3). For example, A. niger encodes 22 GH28 (polygalac-turonase) enzymes (78, 91, 133); N. crassa and M. thermophila have only two (14, 15). However, aswith the PMO/GH61 genes, the expression level of genes encoding GH28 enzymes under plantbiomass conditions is very similar among different lamentous ascomycete species (14, 27, 31,127) (Figure 3).

REGULATORY MECHANISMS

Carbon Catabolite Repression

Easily metabolized carbon sources such as glucose and sucrose are used preferentially over plantbiomass, a phenomenon called carbon catabolite repression (CCR). CCR affects production ofhydrolytic enzymes in T. reesei, Aspergillus spp., and N. crassa (7, 101, 123). Under conditionsof starvation, the derepression of genes encoding cellulase, hemicellulase, and pectin-degradingenzymes results in a low expression level (27, 31, 43, 78, 83).These secreted enzymes are believed tofunction as scouts that, in the presence plant biomass, producemonomeric and/or small polymericsugars that are subsequently transported into the cell via membrane-bound transporters. These


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Inducer: chemicalcompound thatinitiates geneexpression upondetection/uptake

Ubiquitin pathway:ubiquitin-activating(E1), ubiquitin-conjugating (E2), andubiquitin-ligating (E3)enzymes act in acascade to targetproteins fordegradation or toregulate their activity

Carbohydrate ActiveenZyme (CAZyme):carbohydrate-activecatalytic andcarbohydrate bindingenzymes that degrade,modify, or createglycosidic bonds

Cellodextrins:-1,4-linked glucosepolymers of varyinglengths resulting fromdeconstruction ofcellulose

sugars can function as signaling molecules that induce high expression of genes encoding enzymesrequired for plant biomass deconstruction. Signal transduction could occur during or via transportof sugars into the cell, or by the sugars or metabolites derived from them acting inside the cell toinduce the full repertoire of a broad range of enzymes/proteins required for utilization of plantmaterial.

Some aspects ofCCR inlamentous fungi aremediated by a conserved zinc-nger transcriptionfactor (CreA/Cre1) that functions primarily as a repressor of lignocellulolytic genes (38, 101, 119).In Aspergillus spp., CreA regulates genes involved in xylose, xylan, cellulose, arabinose, proline,and ethanol utilization (reviewed in 29). In T. reesei and N. crassa, CRE1/CRE-1 regulates bothxylan and cellulose utilization (73, 96, 123, 144). However, deletion of creA homologs does notinduce the expression of lignocellulolytic genes in the absence of an inducer derived from plantcell wall material (such as cellobiose or xylose; see below). CreA/CRE1 regulates transcriptionof genes in a double-lock manner. For example, in Aspergillus spp., CreA represses transcriptionof xlnR, which encodes a transcription factor that regulates genes encoding enzymes involved inxylan utilization, as well as represses genes encoding the enzymes themselves (xlnA) (30, 89, 126).

In addition to transcriptional repression, ubiquitination, which functions in protein turnover,assembly and function, is involved in CCR in A. nidulans and T. reesei (70). In T. reesei, theubiquitin C-terminal hydrolase CRE2 and the E3 ubiquitin ligase LIM1 play a role in regulationof cellulase gene expression (33, 51). However, the targets of the ubiquitin pathway have not yetbeen identied, nor is it clear whether the ubiquitinylated factor is destined for degradation bythe proteasome or if ubiquitinylation causes a signal-specic activation (137).

Chromatin

In lamentous fungi, the effects of chromatin remodeling onmetabolic processes have been studiedin Aspergillus spp. and Fusariumwith respect to nitrogen (13) and secondary metabolism (reviewedin 45). In T. reesei, the Hap2/3/5 complex, CRE1, and an unknown GTAATA binding proteinaffect nucleosome positioning, thus inuencing accessibility of the TATA box for transcriptioninitiation (140, 141). InA. nidulans, CreA function is dependent on histone acetylation status aswellas on GcnE, a homolog of the Saccharomyces cerevisiae histone acetyltransferase GCN5 (47, 99), animportant coactivator for positive and negative transcriptional regulation. In T. reesei, an enrich-ment for expression of genes related to gcn5 was correlated with increased protein production (9).

In many lamentous ascomycete species, genes involved in the production of secondarymetabolites are found in coregulated gene clusters (16). In A. nidulans, regulation of secondarymetabolic clusters is affected by LaeA, a predicted protein methyltransferase (120). Unlike inother lamentous ascomycete fungi, in T. reesei, CAZyme-encoding genes are also frequentlyfound in clusters with genes involved in production of secondary metabolites (80). Importantly,the homolog of laeA in T. reesei (lae1) is essential for expression of 50 CAZyme-encoding genes,including glycoside hydrolases involved in both cellulose and hemicellulose degradation (114).

Transcription Factors Involved in Cellulose Deconstruction

The action of cellulases on cellulose microbrils results in the formation of cellobiose andhigher-order oligosaccharides (cellodextrins) (Figure 1). A low concentration of cellobioseinduces cellulase gene expression and activity in T. reesei (132), Aspergillus spp. (26), andN. crassa (39). InN. crassa, a strain carrying deletions for the three major -glucosidase genes (thuspreventing almost all conversion of cellobiose into glucose) results in the induction of cellulases inresponse to cellobiose (144). The induction of genes/enzymes in the triple -glucosidase mutant

484 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Transglycosylation:the transfer of a sugarresidue from oneglycoside to another

Avicel: proprietaryname formicrocrystallinecellulose

Regulon: gene setregulated directly orindirectly by atranscription factor;most often determinedby expressiondifferences inwild-type versustranscription factormutant strain

recapitulates the wild-type response to crystalline cellulose. In T. reesei, the oligosaccharidesophorose, which can be generated by the transglycosylation of cellobiose by -glucosidaseenzymes, acts as a potent inducer of cellulases (118). Sophorose does not induce expression ofcellulolytic genes in N. crassa or other lamentous fungi (49, 144). However, recent work in aT. reesei strain suggests that cellobiose, not sophorose, may be the natural inducing molecule(143). In addition, unlike in other lamentous fungi, lactose induces cellulase gene expression inT. reesei, although apparently via a mechanism other than on sophorose (113).

In T. reesei, 220 genes predicted to encode carbohydrate-modifying enzymes are inducedupon growth on lactose, sophorose, cellulose, or plant biomass (44, 53). In A. niger, 65% ofmRNA-encoding CAZymes under lignocellulosic conditions are composed of ve families: GH7,GH11, GH61, GH62, and CE1 (cellobiohydrolases, xylanases, PMOs, arabinofuranosidases, andacetyl esterases, respectively) (31) (Figure 3). WhenN. crassa is exposed to Avicel, 212 genes aredifferentially upregulated (Avicel regulon) (27, 144) (Figure 3). More than 50% of the proteinsencoded by these 212 genes are predicted to enter the secretory pathway (27), including 17 of 21predicted cellulase genes and 11 of 19 predicted hemicellulase genes in theN. crassa genome (127).As in other lamentous ascomycete fungi, a large number of genes encoding hypothetical proteinsare coregulated with lignocellulolytic genes in N. crassa (127). A number of these hypotheticalproteins are predicted to be secreted and have in fact been identied in secretomes of fungiexposed to plant biomass (2, 127, 131). These observations suggest that many of these proteinsfunction in some capacity for plant biomass deconstruction.

InT. reesei andAspergillus spp., the transcriptional regulatorXYR1/XlnR regulates expression ofhemicellulase and cellulase genes, respectively (76, 86, 121) (Figure 4). Strains carrying a deletionof xyr1 in T. reesei or an A. oryzae xlnR mutant are decient for xylanase and cellulase activity (86,121). In T. reesei, a nonconserved transcriptional activator, ACE2 (8), and the repressor ACE1 (6)also regulate cellulase gene expression. In N. crassa and Fusarium oxysporum, the xlnR homolog isrequired for xylan utilization (see below) but only modulates cellulase gene expression and activity(18, 20, 124).

In N. crassa, two conserved transcription factor genes [cellulose degradation regulator (clr)-1 and clr-2] are required for growth specically on crystalline cellulose (27) (Figure 4). Thefunction of clr-2 in regulating cellulase gene expression is conserved in A. nidulans (27). CLR-1/CLR-2 regulate 135 genes of the 210 Avicel regulon, including cellulase and hemicellulasegenes, genes encoding cellodextrin transporters, and genes likely to be involved in degradingmorecomplex sources of lignocellulose including mannan, pectin, and arabinose. The CLR-1/CLR-2regulon also includes 55 hypothetical proteins, whose role in cellulose deconstruction has yet tobe examined.

A novel transcription factor identied in A. aculeatus, ClbR, is involved in XlnR-independentcellobiose and cellulose induction of cbh1 (GH7) and cmc2 (endoglucanase) (66) (Figure 4). InT. reesei, an additional conserved transcriptional regulator, BglR, was identied that specicallyregulates genes encoding -glucosidase enzymes (with the exception of bgl1) (85). The role ofBglR in other species during plant biomass deconstruction has not yet been examined.

Transcription Factors Involved in Hemicellulose and Pectin Deconstruction

Loss-of-function mutants in xlnR in A. niger exhibit strongly reduced xylanolytic activities (134),and 10 genes involved in the degradation of xylan and cellulose are regulated by XlnR, includingcellobiohydrolase genes (cbhA and cbhB) (49), endoglucanase genes (eglA and eglB), xylanase genes(xlnB, xlnC, and xlnD), and xylose metabolism genes (xyrA; xylose reductase) (56). Similarly, inT. reesei, XYR1 regulates cellulase, hemicellulase, and xylose metabolism genes (121) (Figure 4).


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


?

?

gh54-1gh3-7 gh43-2 xr----gh35-2 ce5-2 gh11-2gh10-1

gh67-1 ce1-1cdt-2gh11-1cdh-1gh61-2

cbh-1

cbh-2

gh5-1--------gh3-4

gh1-1

gh3-3gh3-6--------

gh5-7

abf1bxl1----xyl1xyn1bga1axe1xyn2xyn3

grl1----46819--------egl4

cbh1

cbh2

----eg2----bgl1bgl2cel1bcel3b----cel3ccel3d

man1

abfBxlnDxynDxyrA----lacA--------xlnC

aguAaxeA8347xlnB7230gh61acbhAcbhBcbhDcbhCeglA----eglC----bgl410375--------bglKbglH

man5a

Neurospora Trichoderma Aspergillus

Complexsubstrates Xylan

CellobioseSophorose

Cellulose

Xylose

Strict dependenceRepression

Modulation

No induction

XLR-1

ClbR Partial dependence

XLR-1

CLR-1 CLR-2Xyr1

BglR

ACE1 ?

?Clr2

Clr1 ?

?BglR

ACE1

ACE1

ACE1

BglR

ClbR

XlnR

ClrA

ClrB

Figure 4Transcriptional regulation of genes encoding plant cell walldegrading enzymes. Model of induction of major fungal hydrolyticenzymes by soluble inducers in Neurospora crassa (27, 124, 144), Trichoderma reesei (8, 85), and Aspergillus species (A. niger, A. nidulans,and A. aculeatus) (27, 31, 66). Horizontally aligned genes are likely orthologs listed by gene names as given in the Broad Institutedatabase (N. crassa; http://www.broadinstitute.org/annotation/genome/neurospora/MultiHome.html), Uniprot (T. reesei;http://www.uniprot.org), or AspGD (Aspergillus spp.; http://www.aspgd.org). For T. reesei and Aspergillus genes lacking a commonname, Joint Genome Institute protein IDs (T. reesei; http://genome.jgi-psf.org/Trire2/Trire2.home.html) or AspGD (A. nidulans)gene names are given. Arrows passing through a regulator represent a strict requirement for a functional copy of that regulator forspecic induction. Nodes intersecting an inductive pathway indicate a modulation of specic induction. Lack of an indicatedrelationship does not necessarily imply a reported negative result, as systematic public datasets are few, particularly for regulatorymutant strains.

In contrast to Aspergillus spp. and T. reesei, xlnR homologs in N. crassa (xlr-1) and Fusariumspp. (xlnR) are only required for xylan/xylose utilization (18, 20, 124) (Figure 4). In N. crassa,only 30 genes are induced by exposure to xylose, most of which are involved in xylose utilization,whereas the expression of 245 genes under hemicellulose conditions is dependent on xlr-1(124). Microarray analysis of A. oryzae showed that AoXlnR regulates 75 genes during growthon beechwood xylan (86). Of these, 19 genes were conserved between the A. oryzae XlnR andN. crassa XLR-1 regulons, including genes encoding conserved metabolic enzymes involved inxylose metabolism, hemicellulase genes (arabinofuranosidase, endoxylanase, and -xylosidase),and transporters (124). However, in N. crassa, the gene set induced by exposure to xylan versusthe gene set dependent upon XLR-1 does not completely overlap, indicating that unknowntranscription factors regulate additional genes involved in hemicellulose deconstruction.

486 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Per, Arnt, and Sim(PAS) domain:protein domain foundin proteins thatfunction as sensorymodules for light,redox, or oxygentension

In A. niger, a number of genes encoding enzymes involved in pectin utilization, including poly-galacturonase ( pgaD), a rhamnogalacturonan lyase (rglA), and several genes encoding rhamno-galacturonan side-chain-degrading enzymes (abnA, abnC, abfB, faeB, and lacE) (78), are derepressedunder starvation conditions. The induction of additional pectinolytic genes is likely responsive to anumber of different metabolites, such as galacturonic acid, rhamnose, arabinose, galactose, xylose,and ferulic acid (28, 79). Unlike cellulose and hemicellose degradation in lamentous ascomycetefungi, specic transcription factors required for the induction of pectinolytic enzymes have not yetbeen identied, suggesting that induction of these genes is regulated by amultifactorial system (28).

Antisense Transcription

Regulation of gene expression by natural antisense transcription is a well-known phenomenonin fungi (50, 84, 88). In A. niger, 2% of RNA-Seq reads correlate with antisense transcripts,and a marked antisense-sense switch between growth on glucose and growth on wheat strawwas observed for many of them. The switch in the antisense/sense ratio was abolished in a creAstrain, suggesting thatCreAdirectly or indirectly regulates the antisense/sense ratio under differentcarbon conditions (31).

Crosstalk Between Regulatory Pathways

In A. nidulans, cellulase gene expression is affected by AreA, the global nitrogen transcriptionalregulator (71). InN. crassa, genes encoding proteins involved in amino acid metabolism are withinthe Avicel and CLR-1/CLR-2 regulons (27) as well as the WC-1/WC-2/VVD photoreceptorregulatory network (see below) (108). These observations suggest regulatory crosstalk betweennitrogen, amino acid, and carbonmetabolismduringplant biomass utilizationbylamentous fungi.

Sulfur compounds including cysteine, methionine, and S-adenosylmethionine also affect plantbiomass utilization by lamentous fungi. For example, in T. reesei, the expression of a E3 ubiquitinligase (lim1), which is an ortholog of a negative regulator of sulfur utilization inN. crassa (scon-2) andS. cerevisiae (MET30), is induced when T. reesei is under sulfur limitation or exposed to cellulase-inducing conditions (51); LIM1 binds to the promoter of the cellobiohydrolase gene cbh2.

ENVIRONMENTAL AND DEVELOPMENTAL REGULATIONOF PLANT CELL WALLDEGRADING CAPACITY

Light

Filamentous fungi rapidly and efciently react to evenminute amounts of light (10, 105), which canaffect developmental processes, morphology, andmetabolic pathways (103, 130). At the molecularlevel these responses are due mainly to homologs of theN. crassa blue-light photoreceptors, whichconsist of a complex of PAS (Per, Arnt, and Sim) domain proteins called white collar-1 (WC-1)and white collar-2 (WC-2) (White Collar Complex, WCC). The WCC regulates a broad array ofgenes via a hierarchical network (116) and is regulated by phosphorylation and protein turnover aswell as by the third photoreceptor, Vivid (VVD). VVD functions in photoadaptation (for a review,see 104). Homologs of wc-1 and wc-2 are highly conserved in lamentous ascomycetes, althoughsome species, such as Aspergillus spp., do not possess orthologs of VVD.

In T. reesei, a genome-wide transcriptome study revealed a considerable number of glycosidehydrolases to be differentially expressed in light versus dark conditions (128). In N. crassa, WC-1,WC-2, and VVD as well as their homologs in T. reesei (BLR1, BLR2, and ENV1, respectively)


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


xyr1

gna1

gna3

cbh1cbh2

LL DD

ACY1

BLR2

BLR1

PDE cAMP

PhLP1

GNB1 GNG1

GNA1ENV1

PKAC1

GNA3

P

Expression of plantcell walldegrading

enzymes

Trichodermareesei

Light responsiveness

of geneexpression

Light Nutrients pHgg

X

Figure 5Environmental regulation of enzymes/genes involved in plant cell wall deconstruction. Regulatoryinteractions of signaling components are shown as identied in Trichoderma reesei. X indicates the yetunidentied regulator of xyr1 transcription, which is the putative target of PKAC1. Arrows indicate positiveinuence on transcript abundance, whereas plungers indicate negative inuence on transcript abundance.Dashed arrows and plungers indicate hypothesized effects. Abbreviations: LL, constant light; DD, constantdarkness.

positively regulate cellulase gene transcription (23, 106, 108) (Figure 5). The positive transcrip-tional regulation is paralleled by a negative effect on total cellulolytic activity produced by therespective mutants, suggesting a role for posttranslational mechanisms during light-regulatedcellulase production (52, 108, 110).

InN. crassa, theWCCbinds to the promoter region of clr-1 (116), which encodes a transcriptionfactor required for cellulose utilization (see above; 27). In T. reesei, strains containing mutationsin components of other signal transduction pathways, such as heterotrimeric G proteins (genesencoding G-protein or subunit or the class I phosducin-like protein, PhLP1), show a largeincrease in the number of light-regulated genes (129). Similarly, the cAMP pathway also affectslight-modulated cellulase gene expression in T. reesei (111).

488 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Heterotrimeric G-Protein Pathway

Fungi have signaling cascades for reception and transmission of information on the chemi-cal composition of the substrates in the environment. The heterotrimeric guanine-nucleotide-binding protein (G-protein , , and subunits) pathway comprises transmembrane receptorsas well as regulatory proteins [regulators of G-protein signaling (RGS) proteins or phosducin-like proteins] (68). Output pathways include the cAMP pathway and mitogen-activated pro-tein kinase (MAPK) pathways (Figure 5). A role for G-protein signaling in cellulase gene ex-pression was rst described in the chestnut tree pathogen, Cryphonectria parasitica; lack of theG-protein subunit CPG-1 abolished cellulase induction (135). In T. reesei, two G-protein subunits, GNA1 and GNA3, regulate cellulase gene expression in a light-dependent mannerbut do not enable inducer-independent cellulase production. Constitutive activation of GNA3positively inuences cellulase gene expression in light, whereas deletion of gna1 causes stronglyincreased cellulase gene expression in darkness but abolishes this process in light (107, 112).Mutants carrying a deletion of the G-protein (GNB1) or (GNG1) subunits or of PhLP1of T. reesei, predicted to act as a cochaperone for G-protein and folding, show decreasedcellulase gene transcription but increased production of cellulolytic enzymes (129). In A. niger,the expression of a homolog of a PTH11-type G-protein-coupled receptor upon exposure tocellulosic material suggests the involvement of G-protein signaling in cellulase gene regulation(31).

Because G-protein subunits and G-protein-coupled receptors of fungi do not respond tolight, the light-dependent effect must be introduced by a different pathway. For T. reesei, the lightregulatory protein ENVOY (VVD) was shown to negatively regulate transcription of gna3 and topositively contribute to feedback regulation of gna1 transcription (Figure 5). PhLP1 is connectedwith ENVOY, which constitutes a node between light response and heterotrimeric G-proteinsignaling (107, 128).

cAMP Pathway

The secondary messenger cAMP regulates a variety of processes in fungi and is produced inresponse to extracellular stimuli. Cellular cAMP levels are adjusted by a balance of biosynthe-sis (by adenylate cyclase) and degradation (by phosphodiesterases). The primary target of thispathway is cAMP-dependent protein kinase A (PKA), which mediates the effects of cAMP byphosphorylation of regulator proteins (36). A regulatory inuence of the cAMP pathway on plantcell wall degradation in Trichoderma, Penicillium, and Aspergillus spp. has been described (35, 41).Low amounts of cAMP stimulate cellulase activity, whereas high levels of cAMP repress cellulaseformation. Similar to other regulatory pathways, cAMP does not induce cellulases in the absenceof an inducer derived from plant cell wall material (35, 115).

In N. crassa, constitutive activation of PKA by removal of the regulatory subunit (mcb) resultsin a mutant that shows apolar growth and increased secretion of cellulases (67). For T. reesei, PKAand adenylate cyclase (ACY1) are involved in the regulation of cellulase gene expression, with anunknown regulator of xyr1 as the likely target (111).

cAMP levels are strongly decreased in mutants lacking ENV1, and their growth phenotype inlight is alleviated by the addition of a phosphodiesterase inhibitor. Consequently, ENV1 is likelyto affect the cAMP pathway and hence cellulase gene expression at least in part by dampeningphosphodiesterase activity (128) (Figure 5). In T. reesei, a RAS GTPase (trRas2) was reported tobe involved in cAMP signaling andmodulation of cellulase gene expression and to affect regulationof XYR1 in a cAMP-independent manner (142).


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


Arrestin: protein thatregulates activity ofG-protein-coupledreceptors after theirphosphorylation; alsobinds to otherreceptors and signalingproteins

Peptide pheromone:small peptides actingas messengers for thepresence of a potentialmating partner;important for sexualdevelopment

pH

The pH response in lamentous fungi is mediated by the conserved transcription factor PacC(reviewed in 32, 92), which functions as an activator of genes expressed in alkaline conditionsand as a repressor under acidic conditions. The pH response is mediated by the G-protein-coupled receptor PalH and the arrestin PalF, possibly connecting to cellulase regulation viaG-protein subunits (see above). PacC inuences expression of xylanases (72), an arabinofu-ranosidase (48), and endopolygalacturonases (100, 122). In N. crassa, deletion of pacC causes agrowth defect on cellulose (27). In T. reesei, the expression optima of cellulolytic enzymes varywith pH and the maximum efciency of cellulose degradation occurs at pH 5.0 (3). In general,different fungi have different pH optima for efcient production of cellulolytic enzymes, andgene regulation in response to pH appears to be aimed at a delicate balance between substratedegradation, uptake of the resulting sugar, metabolic activity, and enzyme activity (39, 77, 118,132).

Development

If the environmental conditions, especially nutritional conditions, in the habitat of a fungus de-teriorate, asexual and sexual development are meant to secure the survival of the species (1). InT. reesei, expression of genes encoding plant cell walldegrading enzymes is associated with theonset of conidiation (81) and asexual spores of T. reesei have cellulases associated with the fun-gal cell wall (65). In T. reesei, transcription of genes involved in plant cell wall degradation wascorrelated with sexual development (24). In particular, a peptide pheromone gene, hpp1, was dif-ferentially expressed between a strain producing a high level of cellulases versus one defective incellulase production (109). In N. crassa, mutants lacking the pheromone gene ppg-1 show lowercellulase activity than a wild-type strain (108), suggesting a connection between sexual devel-opment and plant cell wall deconstruction may be widespread among lamentous ascomycetefungi.

CONCLUSIONS

The coordinated induction of plant cell walldegrading enzymes is responsive to detection ofa variety of individual components of plant biomass; the identity of signaling compounds andthe mechanism by which transcriptional induction occurs is not clear. In addition to regulationof gene expression by transcription factors, recent studies highlight novel perspectives for re-search toward improvement of enzyme production and secretion in lamentous fungi includingchromatin regulation and natural antisense transcription. Comparative genomic and transcrip-tional analyses of the plant cell wall degradation repertoire of lamentous fungi have revealedboth conserved and divergent components, presumably reecting the different ecological nichesof these organisms in nature. Future studies combining comparative transcriptional and pro-teomic analyses should yield new fundamental insights into how different fungi grow on plantbiomass. The wealth of yet uncharacterized genes, which are coregulated with plant cell walldegrading enzymes or signicantly regulated and expressed under inducing conditions, are likelyto reveal novel accessory proteins. The characterization of these novel factors will enable theelucidation of associated biochemical mechanisms that could increase the efciency of plant cellwall degradation and may expedite development of tailor-made enzyme cocktails for particularfeedstocks.

490 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


SUMMARY POINTS

1. Induction of plant cell walldegrading enzymes occurs after sensing or uptake of low-molecular-weight compounds resulting from deconstruction of cellulose, hemicellulose,and pectin.

2. Despite conservation of some transcription factors responsible for the regulation of plantcell walldegrading enzymes, the mechanisms and components of the genomic inventoryfor this process are diverse in different fungi.

3. Hydrolytic enzymes are not only induced in response to the presence of plant cell wallmaterial, but are also regulated by CCR, chromatin remodeling, and natural antisensetranscripts.

4. Nutrient-signaling pathways are interrelated with the light response pathway, whichcauses plant cell walldegrading enzymes to be regulated differentially in light versusdarkness, although the presence of an inducer is still required.

5. The number of genes encoding CAZymes varies in fungi and appears to reect their pre-ferred habitat. Nevertheless, the extent of expression of these genes does not necessarilycorrelate with their abundance in the genome.

6. Oxidative cleavage of cellulose by polysaccharide monooxygenases and cellobiose dehy-drogenases has emerged as an important contribution to plant cell wall degradation.

FUTURE ISSUES

1. Asmore fungal genomes are sequenced and as transcriptome, proteome, andmetabolomedatasets become available, the next step is to identify conserved pathways and functionsspecically dedicated to plant cell wall deconstruction.

2. Biochemical and structural characterization of proteins of unknown function that aresecreted with plant cell walldegrading enzymes should be determined.

3. The environmental and nutrient-sensing signaling pathways should be integrated withregulation of genes encoding plant cell walldegrading enzymes by substrate-specictranscription factors.

4. Crosstalk between polysaccharide metabolism and other metabolic pathways as well astheir relevance for plant cell wall degradation should be determined.

5. Oxidative degradation of cellulose must be evaluated for its impact on the fungal celland the signal transduction pathways responsible for the regulation of plant cell walldegradation.

DISCLOSURE STATEMENT

Dr. Glass and Dr. Cate have led patent applications related to some of the pathways coveredin this review. Published patent applications include Methods and Compositions for ImprovingSugar Transport, Mixed Sugar Fermentation, and Production of Biofuels (WO2011011796).


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


ACKNOWLEDGMENTS

We thank Dr. Johan Philipp Benz for comments on the manuscript.

LITERATURE CITED

1. AanenDK,HoekstraRF. 2007.Why sex is good. InSex in Fungi:MolecularDetermination and EvolutionaryImplications, ed. J Heitman, JW Kronstad, JW Taylor, L Casselton, pp. 52734. Washington, DC: ASMPress

2. Adav SS, Chao LT, Sze SK. 2012. Quantitative secretomic analysis of Trichoderma reesei strains revealsenzymatic composition for lignocellulosic biomass degradation. Mol. Cell. Proteomics 11:M111.012419

3. Adav SS, Ravindran A, Chao LT, Tan L, Singh S, Sze SK. 2011. Proteomic analysis of pH and strainsdependent protein secretion of Trichoderma reesei. J. Proteome Res. 10:457996

4. Andersen MR, Vongsangnak W, Panagiotou G, Salazar MP, Lehmann L, Nielsen J. 2008. A trispeciesAspergillusmicroarray: comparative transcriptomics of threeAspergillus species. Proc. Natl. Acad. Sci. USA105:438792

5. Arnaud MB, Chibucos MC, Costanzo MC, Crabtree J, Inglis DO, et al. 2010. The Aspergillus GenomeDatabase, a curated comparative genomics resource for gene, protein and sequence information for theAspergillus research community. Nucleic Acids Res. 38:42027

6. Aro N, Ilmen M, Saloheimo A, Penttila M. 2003. ACEI of Trichoderma reesei is a repressor of cellulaseand xylanase expression. Appl. Environ. Microbiol. 69:5665

7. Aro N, Pakula T, Penttila M. 2005. Transcriptional regulation of plant cell wall degradation by lamen-tous fungi. FEMS Microbiol. Rev. 29:71939

8. Aro N, Saloheimo A, Ilmen M, Penttila M. 2001. ACEII, a novel transcriptional activator involved inregulation of cellulase and xylanase genes of Trichoderma reesei. J. Biol. Chem. 276:2430914

9. Arvas M, Pakula T, Smit B, Rautio J, Koivistoinen H, et al. 2011. Correlation of gene expression andprotein production ratea system wide study. BMC Genomics 12:616

10. Baker CL, Loros JJ, Dunlap JC. 2011. The circadian clock of Neurospora crassa. FEMS Microbiol. Rev.36:95110

11. Bastawde KB. 1992. Xylan structure, microbial xylanases, and their mode of action. World J. Microbiol.Biotechnol. 8:35368

12. Beeson WT, Phillips CM, Cate JHD, Marletta MA. 2012. Oxidative cleavage of cellulose by fungalcopper-dependent polysaccharide monooxygenases. J. Am. Chem. Soc. 134:89092

13. Berger H, Basheer A, Bock S, Reyes-Dominguez Y, Dalik T, et al. 2008. Dissecting individual stepsof nitrogen transcription factor cooperation in the Aspergillus nidulans nitrate cluster. Mol. Microbiol.69:138598

14. Berka RM, Grigoriev IV, Otillar R, Salamov A, Grimwood J, et al. 2011. Comparative genomic analysisof the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris. Nat.Biotechnol. 29:92227

15. BorkovichKA,AlexLA,YardenO,FreitagM,TurnerGE, et al. 2004.Lessons from thegenome sequenceof Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol. Mol.Biol. Rev. 68:1108

16. Brakhage AA. 2013. Regulation of fungal secondary metabolism. Nat. Rev. Microbiol. 11:213217. Broad Institute. 2013. Chaetomium globosum database. http://www.broadinstitute.org/annotation/

genome/chaetomium_globosum/Home.html18. Brunner K, Lichtenauer AM, Kratochwill K, Delic M, Mach RL. 2007. Xyr1 regulates xylanase but not

cellulase formation in the head blight fungus Fusarium graminearum. Curr. Genet. 52:2132019. Caffall KH, Mohnen D. 2009. The structure, function, and biosynthesis of plant cell wall pectic polysac-

charides. Carbohydr. Res. 344:187990020. Calero-Nieto F, Di Pietro A, Roncero MI, Hera C. 2007. Role of the transcriptional activator xlnR of

Fusarium oxysporum in regulation of xylanase genes and virulence. Mol. Plant Microbe Interact. 20:9778521. Cantarel BL, Coutinho PM, Rancurel C, BernardT, LombardV,Henrissat B. 2009. TheCarbohydrate-

Active EnZymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res. 37:23338

492 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


22. Carroll A, Somerville C. 2009. Cellulosic biofuels. Annu. Rev. Plant Biol. 60:1658223. Castellanos F, Schmoll M, Martinez P, Tisch D, Kubicek CP, et al. 2010. Crucial factors of the light

perception machinery and their impact on growth and cellulase gene transcription in Trichoderma reesei.Fungal Genet. Biol. 47:46876

24. Chen CL, Kuo HC, Tung SY, Hsu PW, Wang CL, et al. 2012. Blue light acts as a double-edged swordin regulating sexual development of Hypocrea jecorina (Trichoderma reesei ). PLoS One 7:e44969

25. Chen XA, Ishida N, Todaka N, Nakamura R, Maruyama J, et al. 2010. Promotion of efcient sacchari-cation of crystalline cellulose by Aspergillus fumigatus Swo1. Appl. Environ. Microbiol. 76:255661

26. ChikamatsuG, Shirai K, KatoM,Kobayashi T,TsukagoshiN. 1999. Structure and expression propertiesof the endo--1,4-glucanase A gene from the lamentous fungus Aspergillus nidulans. FEMS Microbiol.Lett. 175:23945

27. Coradetti ST, Craig JP, Xiong Y, Shock T, Tian C, Glass NL. 2012. Conserved and essential transcrip-tion factors for cellulase gene expression in ascomycete fungi. Proc. Natl. Acad. Sci. USA 109:7397402

28. deVries RP, Jansen J, AguilarG, Parenicova L, JoostenV, et al. 2002. Expression proling of pectinolyticgenes from Aspergillus niger. FEBS Lett. 530:4147

29. deVries RP, Visser J. 2001.Aspergillus enzymes involved in degradation of plant cell wall polysaccharides.Microbiol. Mol. Biol. Rev. 65:497522

30. de Vries RP, Visser J, de Graaff LH. 1999. CreA modulates the XlnR-induced expression on xylose ofAspergillus niger genes involved in xylan degradation. Res. Microbiol. 150:28185

31. Delmas S, Pullan ST, Gaddipati S, Kokolski M, Malla S, et al. 2012. Uncovering the genome-wide tran-scriptional responses of the lamentous fungusAspergillus niger to lignocellulose using RNA sequencing.PLoS Genet. 8:e1002875

32. Denison SH. 2000. pH regulation of gene expression in fungi. Fungal Genet. Biol. 29:617133. Denton JA, Kelly JM. 2011. Disruption of Trichoderma reesei cre2, encoding an ubiquitin C-terminal

hydrolase, results in increased cellulase activity. BMC Biotechnol. 11:10334. Dodd D, Cann IKO. 2009. Enzymatic deconstruction of xylan for biofuel production. GCB Bioenergy

1:21735. DongW,Qu YB, Gao PJ. 1995. Regulation of cellulase synthesis in mycelial fungi: participation of ATP

and cyclic-AMP. Biotechnol. Lett. 17:5939836. DSouza CA, Heitman J. 2001. Conserved cAMP signaling cascades regulate fungal development and

virulence. FEMS Microbiol. Rev. 25:3496437. Dunlap JC, Borkovich KA, Henn MR, Turner GE, Sachs MS, et al. 2007. Enabling a community to

dissect an organism: overview of the Neurospora functional genomics project. Adv. Genet. 57:499638. Ebbole DJ. 1998. Carbon catabolite repression of gene expression and conidiation in Neurospora crassa.

Fungal Genet. Biol. 25:152139. Eberhart BM, Beck RS, Goolsby KM. 1977. Cellulase of Neurospora crassa. J. Bacteriol. 130:1818640. Eijsink VG, Vaaje-Kolstad G, Varum KM, Horn SJ. 2008. Towards new enzymes for biofuels: lessons

from chitinase research. Trends Biotechnol. 26:2283541. Farkas V,GresikM,KolarovaN, Sulova Z, Sestak S. 1989. Biochemical and physiological changes during

photo-induced conidiation and derepression of cellulase synthesis in Trichoderma. In Trichoderma reeseiCellulase: Biochemistry, Genetics, Physiology, and Application, ed. CP Kubicek, DE Eveleigh, W Esterbauer,W Steiner, EM Kubicek-Pranz, pp. 13955. Cambridge, UK: Graham House

42. Field CB, Behrenfeld MJ, Randerson JT, Falkowski P. 1998. Primary production of the biosphere:integrating terrestrial and oceanic components. Science 281:23740

43. Flipphi M, Felenbok B. 2004. The onset of carbon catabolite repression and interplay between specicinduction and carbon catabolite repression in Aspergillus nidulans. In Biochemistry and Molecular Biology,ed. R Brambl, GA Marzluf, 3:40320. Berlin/Heidelberg: Springer

44. Foreman PK, Brown D, Dankmeyer L, Dean R, Diener S, et al. 2003. Transcriptional regulation ofbiomass-degrading enzymes in the lamentous fungus Trichoderma reesei. J. Biol. Chem. 278:3198897

45. Gacek A, Strauss J. 2012. The chromatin code of fungal secondary metabolite gene clusters. Appl.Microbiol. Biotechnol. 95:1389404

46. Galagan JE, Calvo SE, Borkovich KA, Selker EU, Read ND, et al. 2003. The genome sequence of thelamentous fungus Neurospora crassa. Nature 422:85968


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


47. Garcia I, Gonzalez R, Gomez D, Scazzocchio C. 2004. Chromatin rearrangements in the prnD-prnBbidirectional promoter: dependence on transcription factors. Eukaryot. Cell 3:14456

48. Gielkens M, Gonzalez-Candelas L, Sanchez-Torres P, van de Vondervoort P, de Graaff L, et al. 1999.The abfB gene encoding the major-L-arabinofuranosidase of Aspergillus nidulans: nucleotide sequence,regulation and construction of a disrupted strain. Microbiology 145:73541

49. Gielkens MM, Dekkers E, Visser J, de Graaff LH. 1999. Two cellobiohydrolase-encoding genes fromAspergillus niger require D-xylose and the xylanolytic transcriptional activator XlnR for their expression.Appl. Environ. Microbiol. 65:434045

50. Goodman AJ, Daugharthy ER, Kim J. 2012. Pervasive antisense transcription is evolutionarily conservedin budding yeast. Mol. Biol. Evol. 30:40921

51. GremelG,DorrerM, SchmollM. 2008. Sulphurmetabolism and cellulase gene expression are connectedprocesses in the lamentous fungusHypocrea jecorina (anamorphTrichoderma reesei ).BMCMicrobiol. 8:174

52. Gyalai-Korpos M, Nagy G,Mareczky Z, Schuster A, Reczey K, Schmoll M. 2010. Relevance of the lightsignaling machinery for cellulase expression in Trichoderma reesei (Hypocrea jecorina). BMC Res. Notes3:330

53. Hakkinen M, Arvas M, Oja M, Aro N, Penttila M, et al. 2012. Re-annotation of the CAZy genes ofTrichoderma reesei and transcription in the presence of lignocellulosic substrates.Microb. Cell Fact. 11:134

54. Harholt J, Suttangkakul A, Scheller HV. 2010. Biosynthesis of pectin. Plant Physiol. 153:3849555. Harris PV, Welner D, McFarland KC, Re E, Navarro Poulsen JC, et al. 2010. Stimulation of lignocel-

lulosic biomass hydrolysis by proteins of glycoside hydrolase family 61: structure and function of a large,enigmatic family. Biochemistry 49:330516

56. Hasper AA, Visser J, de Graaff LH. 2000. The Aspergillus niger transcriptional activator XlnR, which isinvolved in the degradation of the polysaccharides xylan and cellulose, also regulates D-xylose reductasegene expression. Mol. Microbiol. 36:193200

57. HimmelME, Bayer EA. 2009. Lignocellulose conversion to biofuels: current challenges, global perspec-tives. Curr. Opin. Biotechnol. 20:31617

58. Horn SJ, Vaaje-Kolstad G, Westereng B, Eijsink VG. 2012. Novel enzymes for the degradation ofcellulose. Biotechnol. Biofuels 5:45

59. Igarashi K, Uchihashi T, Koivula A, Wada M, Kimura S, et al. 2011. Trafc jams reduce hydrolyticefciency of cellulase on cellulose surface. Science 333:127982

60. Jager G, Girfoglio M, Dollo F, Rinaldi R, Bongard H, et al. 2011. How recombinant swollenin fromKluyveromyces lactis affects cellulosic substrates and accelerates their hydrolysis. Biotechnol. Biofuels 4:33

61. Jalak J, Kurasin M, Teugjas H, Valjamae P. 2012. Endo-exo synergism in cellulose hydrolysis revisited.J. Biol. Chem. 287:2880215

62. Karlsson J, Saloheimo A, Siika-Aho M, Tenkanen M, Penttila M, Tjerneld F. 2001. Homologous ex-pression and characterization of Cel61A (EG IV) of Trichoderma reesei. Eur. J. Biochem. 268:6498507

63. Kraulis J, Clore GM, Nilges M, Jones TA, Pettersson G, et al. 1989. Determination of the three-dimensional solution structure of the C-terminal domain of cellobiohydrolase I from Trichoderma reesei.A study using nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing.Biochemistry 28:724157

64. Kubicek CP, Mikus M, Schuster A, Schmoll M, Seiboth B. 2009. Metabolic engineering strategies forthe improvement of cellulase production by Hypocrea jecorina. Biotechnol. Biofuels 2:19

65. Kubicek CP, Muhlbauer G, Grotz M, John E, Kubicek-Pranz EM. 1988. Properties of the conidial-bound cellulase system of Trichoderma reesei. J. Gen. Microbiol. 134:121522

66. Kunitake E, Tani S, Sumitani JI, Kawaguchi T. 2013. A novel transcriptional regulator, ClbR, controlsthe cellobiose- and cellulose-responsive inductionof cellulase and xylanase genes regulatedby twodistinctsignaling pathways in Aspergillus aculeatus. Appl. Microbiol. Biotechnol. 97:201728

67. Lee IH, Walline RG, Plamann M. 1998. Apolar growth of Neurospora crassa leads to increased secretionof extracellular proteins. Mol. Microbiol. 29:20918

68. Li L, Wright SJ, Krystofova S, Park G, Borkovich KA. 2007. Heterotrimeric G protein signaling inlamentous fungi. Annu. Rev. Microbiol. 61:42352

69. Li X, BeesonWT 4th, Phillips CM,MarlettaMA, Cate JH. 2012. Structural basis for substrate targetingand catalysis by fungal polysaccharide monooxygenases. Structure 20:105161

494 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


70. Lockington RA, Kelly JM. 2001. Carbon catabolite repression in Aspergillus nidulans involves deubiqui-tination. Mol. Microbiol. 40:131121

71. Lockington RA, Rodbourn L, Barnett S, Carter CJ, Kelly JM. 2002. Regulation by carbon and nitrogensources of a family of cellulases in Aspergillus nidulans. Fungal Genet. Biol. 37:19096

72. MacCabe AP, Orejas M, Perez-Gonzalez JA, Ramon D. 1998. Opposite patterns of expression of twoAspergillus nidulans xylanase genes with respect to ambient pH. J. Bacteriol. 180:133133

73. Mach RL, Strauss J, Zeilinger S, Schindler M, Kubicek CP. 1996. Carbon catabolite repression ofxylanase I (xyn1) gene expression in Trichoderma reesei. Mol. Microbiol. 21:127381

74. Mach-Aigner AR, Gudynaite-Savitch L, Mach RL. 2011. L-arabitol is the actual inducer of xylanaseexpression in Hypocrea jecorina (Trichoderma reesei ). Appl. Environ. Microbiol. 77:598894

75. Mach-Aigner AR, Pucher ME,Mach RL. 2010. D-xylose as a repressor or inducer of xylanase expressionin Hypocrea jecorina (Trichoderma reesei ). Appl. Environ. Microbiol. 76:177076

76. Mach-Aigner AR, Pucher ME, Steiger MG, Bauer GE, Preis SJ, Mach RL. 2008. Transcriptional regu-lation of xyr1, encoding the main regulator of the xylanolytic and cellulolytic enzyme system in Hypocreajecorina. Appl. Environ. Microbiol. 74:655462

77. Mandels M, Andreotti R. 1978. Problems and challenges in the cellulose to cellulase fermentation.Proc. Biochem. 13:613

78. Martens-UzunovaES, SchaapPJ. 2009.Assessment of thepectin degrading enzymenetworkofAspergillusniger by functional genomics. Fungal Genet. Biol. 46:S17079

79. Martens-Uzunova ES, Zandleven JS, Benen JA, Awad H, Kools HJ, et al. 2006. A new group of exo-acting family 28 glycoside hydrolases of Aspergillus niger that are involved in pectin degradation. Biochem.J. 400:4352

80. MartinezD,BerkaRM,Henrissat B, SaloheimoM,ArvasM, et al. 2008.Genome sequencing and analysisof the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina). Nat. Biotechnol. 26:55360

81. Metz B, Seidl-Seiboth V, Haarmann T, Kopchinskiy A, Lorenz P, et al. 2011. Expression of biomass-degrading enzymes is a major event during conidium development in Trichoderma reesei. Eukaryot. Cell10:152735

82. Mohnen D. 2008. Pectin structure and biosynthesis. Curr. Opin. Plant Biol. 11:2667783. Nakari-Setala T, Paloheimo M, Kallio J, Vehmaanpera J, Penttila M, Saloheimo M. 2009. Genetic

modication of carbon catabolite repression in Trichoderma reesei for improved protein production.Appl. Environ. Microbiol. 75:485360

84. Ni T, Tu K, Wang Z, Song S, Wu H, et al. 2010. The prevalence and regulation of antisense transcriptsin Schizosaccharomyces pombe. PLoS One 5:e15271

85. Nitta M, Furukawa T, Shida Y, Mori K, Kuhara S, et al. 2012. A new Zn(II)2Cys6-type transcriptionfactor BglR regulates -glucosidase expression in Trichoderma reesei. Fungal Genet. Biol. 49:38897

86. Noguchi Y, Sano M, Kanamaru K, Ko T, Takeuchi M, et al. 2009. Genes regulated by AoXlnR, thexylanolytic and cellulolytic transcriptional regulator, in Aspergillus oryzae. Appl. Microbiol. Biotechnol.85:14154

87. Nummi M, Niku-Paavola ML, Lappalainen A, Enari TM, Raunio V. 1983. Cellobiohydrolase fromTrichoderma reesei. Biochem. J. 215:67783

88. Ohm RA, de Jong JF, Lugones LG, Aerts A, Kothe E, et al. 2010. Genome sequence of the modelmushroom Schizophyllum commune. Nat. Biotechnol. 28:95763

89. Orejas M, MacCabe AP, Perez Gonzalez JA, Kumar S, Ramon D. 1999. Carbon catabolite repressionof the Aspergillus nidulans xlnA gene. Mol. Microbiol. 31:17784

90. Pauly M, Keegstra K. 2008. Cell-wall carbohydrates and their modication as a resource for biofuels.Plant J. 54:55968

91. Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, et al. 2007. Genome sequencing and analysisof the versatile cell factory Aspergillus niger CBS 513.88. Nat. Biotechnol. 25:22131

92. Penalva MA, Tilburn J, Bignell E, Arst HN Jr. 2008. Ambient pH gene regulation in fungi: makingconnections. Trends Microbiol. 16:291300

93. Phillips CM, Beeson WT, Cate JH, Marletta MA. 2011. Cellobiose dehydrogenase and a copper-dependent polysaccharide monooxygenase potentiate cellulose degradation by Neurospora crassa. ACSChem. Biol. 6:1399406


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


94. Phillips CM, Iavarone AT, Marletta MA. 2011. Quantitative proteomic approach for cellulose degrada-tion by Neurospora crassa. J. Proteome Res. 10:417785

95. Popper ZA, Michel G, Herve C, Domozych DS, Willats WG, et al. 2011. Evolution and diversity ofplant cell walls: from algae to owering plants. Annu. Rev. Plant Biol. 62:56790

96. Portnoy T, Margeot A, Linke R, Atanasova L, Fekete E, et al. 2011. The CRE1 carbon cataboliterepressor of the fungus Trichoderma reesei: a master regulator of carbon assimilation. BMC Genomics12:269

97. Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, et al. 2012. The Pfam Protein Family Database.Nucleic Acids Res. 40:D290301

98. Quinlan RJ, Sweeney MD, Lo Leggio L, Otten H, Poulsen JC, et al. 2011. Insights into the oxidativedegradation of cellulose by a copper metalloenzyme that exploits biomass components. Proc. Natl. Acad.Sci. USA 108:1507984

99. Reyes-Dominguez Y, Narendja F, Berger H, Gallmetzer A, Fernandez-Martin R, et al. 2008. Nucle-osome positioning and histone H3 acetylation are independent processes in the Aspergillus nidulansprnD-prnB bidirectional promoter. Eukaryot. Cell 7:65663

100. Rollins JA. 2003. The Sclerotinia sclerotiorum pac1 gene is required for sclerotial development and viru-lence. Mol. Plant Microbe Interact. 16:78595

101. Ruijter GJ, Visser J. 1997. Carbon repression in aspergilli. FEMS Microbiol. Lett. 151:10314102. Saloheimo M, Paloheimo M, Hakola S, Pere J, Swanson B, et al. 2002. Swollenin, a Trichoderma reesei

protein with sequence similarity to the plant expansins, exhibits disruption activity on cellulosicmaterials.Eur. J. Biochem. 269:420211

103. SancarG, SancarC, Brugger B,HaN, SachsenheimerT, et al. 2011. A global circadian repressor controlsantiphasic expression of metabolic genes in Neurospora. Mol. Cell 44:68797

104. Schafmeier T, Diernfellner AC. 2011. Light input and processing in the circadian clock of Neurospora.FEBS Lett. 585:146773

105. Schmoll M. 2011. Assessing the relevance of light for fungi implications and insights into the networkof signal transmission. Adv. Appl. Microbiol. 76:2778

106. Schmoll M, Franchi L, Kubicek CP. 2005. Envoy, a PAS/LOV domain protein of Hypocrea jecorina(anamorph Trichoderma reesei ), modulates cellulase gene transcription in response to light. Eukaryot. Cell4:19982007

107. Schmoll M, Schuster A, Silva Rdo N, Kubicek CP. 2009. The G- protein GNA3 of Hypocrea jecorina(anamorph Trichoderma reesei ) regulates cellulase gene expression in the presence of light. Eukaryot. Cell8:41020

108. SchmollM,TianC, Sun J, TischD,GlassNL. 2012.Unravelling themolecular basis for lightmodulatedcellulase gene expression: the role of photoreceptors in Neurospora crassa. BMC Genomics 13:127

109. Schmoll M, Zeilinger S, Mach RL, Kubicek CP. 2004. Cloning of genes expressed early during cellulaseinduction inHypocrea jecorina by a rapid subtraction hybridization approach.Fungal Genet. Biol. 41:87787

110. Schuster A, Kubicek CP, Schmoll M. 2011. Dehydrogenase GRD1 represents a novel component of thecellulase regulon in Trichoderma reesei (Hypocrea jecorina). Appl. Environ. Microbiol. 77:455363

111. Schuster A, Tisch D, Seidl-Seiboth V, Kubicek CP, Schmoll M. 2012. Roles of protein kinase A andadenylate cyclase in light-modulated cellulase regulation in Trichoderma reesei. Appl. Environ. Microbiol.78:216878

112. SeibelC,GremelG, doNascimentoSilvaR, SchusterA,KubicekCP, SchmollM. 2009.Light-dependentroles of the G-protein subunit GNA1 of Hypocrea jecorina (anamorph Trichoderma reesei ). BMC Biol.7:58

113. Seiboth B,Hartl L, PailM, Fekete E, Karaffa L, KubicekCP. 2004. The galactokinase ofHypocrea jecorinais essential for cellulase induction by lactose but dispensable for growth on D-galactose. Mol. Microbiol.51:101525

114. Seiboth B, Karimi RA, Phatale PA, Linke R, Hartl L, et al. 2012. The putative protein methyltransferaseLAE1 controls cellulase gene expression in Trichoderma reesei. Mol. Microbiol. 84:115064

115. Sestak S, Farkas V. 1993. Metabolic regulation of endoglucanase synthesis in Trichoderma reesei: partici-pation of cyclic AMP and glucose-6-phosphate. Can. J. Microbiol. 39:34247

496 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


116. Smith KM, Sancar G, Dekhang R, Sullivan CM, Li S, et al. 2010. Transcription factors in light andcircadian clock signaling networks revealed by genome wide mapping of direct targets for Neurosporawhite collar complex. Eukaryot. Cell 9:154956

117. Somerville C, Bauer S, Brininstool G, Facette M, Hamann T, et al. 2004. Toward a systems approachto understanding plant cell walls. Science 306:220611

118. Sternberg D, Mandels GR. 1979. Induction of cellulolytic enzymes in Trichoderma reesei by sophorose.J. Bacteriol. 139:76169

119. Strauss J, Mach RL, Zeilinger S, Hartler G, Stofer G, et al. 1995. Cre1, the carbon catabolite repressorprotein from Trichoderma reesei. FEBS Lett. 376:1037

120. Strauss J, Reyes-Dominguez Y. 2011. Regulation of secondary metabolism by chromatin structure andepigenetic codes. Fungal Genet. Biol. 48:6269

121. Stricker AR,Grosstessner-HainK,Wurleitner E,MachRL. 2006. Xyr1 (Xylanase Regulator 1) regulatesboth the hydrolytic enzyme system andD-xylosemetabolism inHypocrea jecorina.Eukaryot. Cell 5:212837

122. Suarez T, Penalva MA. 1996. Characterization of a Penicillium chrysogenum gene encoding a PacC tran-scription factor and its binding sites in the divergent pcbAB-pcbC promoter of the penicillin biosyntheticcluster. Mol. Microbiol. 20:52940

123. Sun J, Glass NL. 2011. Identication of the CRE-1 cellulolytic regulon in Neurospora crassa. PLoS One6:e25654

124. Sun J, Tian C, Diamond S, Glass NL. 2012. Deciphering transcriptional regulatory mechanisms asso-ciated with hemicellulose degradation in Neurospora crassa. Eukaryot. Cell 11:48293

125. Sygmund C, Kracher D, Scheiblbrandner S, Zahma K, Felice AK, et al. 2012. Characterization of thetwo Neurospora crassa cellobiose dehydrogenases and their connection to oxidative cellulose degradation.Appl. Environ. Microb. 78:616171

126. Tamayo EN, Villanueva A, Hasper AA, de Graaff LH, Ramon D, Orejas M. 2008. CreA mediatesrepression of the regulatory gene xlnRwhich controls the production of xylanolytic enzymes inAspergillusnidulans. Fungal Genet. Biol. 45:98493

127. Tian C, Beeson WT, Iavarone AT, Sun J, Marletta MA, et al. 2009. Systems analysis of plant cell walldegradation by the model lamentous fungus Neurospora crassa. Proc. Natl. Acad. Sci. USA 106:2215762

128. Tisch D, Kubicek CP, Schmoll M. 2011. New insights into the mechanism of light modulated signalingby heterotrimeric G-proteins: ENVOY acts on gna1 and gna3 and adjusts cAMP levels in Trichodermareesei (Hypocrea jecorina). Fungal Genet. Biol. 48:63140

129. Tisch D, Kubicek CP, Schmoll M. 2011. The phosducin-like protein PhLP1 impacts regulation ofglycoside hydrolases and light response in Trichoderma reesei. BMC Genomics 12:613

130. Tisch D, Schmoll M. 2010. Light regulation of metabolic pathways in fungi. Appl. Microbiol. Biotechnol.85:125977

131. Tsang A, Butler G, Powlowski J, Panisko EA, Baker SE. 2009. Analytical and computational approachesto dene the Aspergillus niger secretome. Fungal Genet. Biol. 46:S15360

132. Vaheri MP, Vaheri MEO, Kauppinen VS. 1979. Formation and release of cellulolytic enzymes duringgrowth of Trichoderma reesei on cellobiose and glycerol. Eur. J. Appl. Microbiol. 8:7380

133. van den Brink J, de Vries RP. 2011. Fungal enzyme sets for plant polysaccharide degradation. Appl.Microbiol. Biotechnol. 91:147792

134. van Peij NN, Gielkens MM, de Vries RP, Visser J, de Graaff LH. 1998. The transcriptional activatorXlnR regulates both xylanolytic and endoglucanase gene expression in Aspergillus niger. Appl. Environ.Microbiol. 64:361519

135. Wang P, Nuss DL. 1995. Induction of a Cryphonectria parasitica cellobiohydrolase I gene is suppressedby hypovirus infection and regulated by a GTP-binding-protein-linked signaling pathway involved infungal pathogenesis. Proc. Natl. Acad. Sci. USA 92:1152933

136. Wang Y, Tang R, Tao J, Gao G, Wang X, et al. 2011. Quantitative investigation of non-hydrolyticdisruptive activity on crystalline cellulose and application to recombinant swollenin. Appl. Microbiol.Biotechnol. 91:135363

137. Welchman RL, Gordon C, Mayer RJ. 2005. Ubiquitin and ubiquitin-like proteins as multifunctionalsignals. Nat. Rev. Mol. Cell. Biol. 6:599609


Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.


138. Yao Q, Sun TT, Liu WF, Chen GJ. 2008. Gene cloning and heterologous expression of a novel en-doglucanase, swollenin, from Trichoderma pseudokoningii S38. Biosci. Biotechnol. Biochem. 72:2799805

139. Youngs H, Somerville C. 2012. Development of feedstocks for cellulosic biofuels. F1000 Biol. Rep. 4:10140. Zeilinger S, Ebner A, Marosits T, Mach R, Kubicek CP. 2001. The Hypocrea jecorina HAP 2/3/5 pro-

tein complex binds to the inverted CCAAT-box (ATTGG) within the cbh2 (cellobiohydrolase II-gene)activating element. Mol. Genet. Genomics 266:5663

141. Zeilinger S, Schmoll M, Pail M,Mach RL, Kubicek CP. 2003. Nucleosome transactions on theHypocreajecorina (Trichoderma reesei ) cellulase promoter cbh2 associated with cellulase induction. Mol. Genet. Ge-nomics 270:4655

142. Zhang J, Zhang Y, Zhong Y, Qu Y, Wang T. 2012. Ras GTPases modulate morphogenesis, sporulationand cellulase gene expression in the cellulolytic fungus Trichoderma reesei. PLoS One 7:e48786

143. Zhou Q, Xu J, Kou Y, Lv X, Zhang X, et al. 2012. Differential involvement of -glucosidases fromHypocrea jecorina in rapid induction of cellulase genes by cellulose and cellobiose. Eukaryot. Cell 11:137181

144. Znameroski EA,Coradetti ST,RocheCM,Tsai JC, IavaroneAT, et al. 2012. Induction of lignocellulose-degrading enzymes in Neurospora crassa by cellodextrins. Proc. Natl. Acad. Sci. USA 109:601217

498 Glass et al.

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.

MI67-FrontMatter ARI 12 August 2013 12:26

Annual Review ofMicrobiology

Volume 67, 2013 Contents

Fifty Years Fused to LacJonathan Beckwith 1

3 Cap-Independent Translation Enhancers of Plant VirusesAnne E. Simon and W. Allen Miller 21

Acyl-Homoserine Lactone Quorum Sensing: From Evolutionto ApplicationMartin Schuster, D. Joseph Sexton, Stephen P. Diggle, and E. Peter Greenberg 43

Mechanisms of Acid Resistance in Escherichia coliUsheer Kanjee and Walid A. Houry 65

The Biology of the PmrA/PmrB Two-Component System: The MajorRegulator of Lipopolysaccharide ModicationsH. Deborah Chen and Eduardo A. Groisman 83

Transcription Regulation at the Core: Similarities Among Bacterial,Archaeal, and Eukaryotic RNA PolymerasesKimberly B. Decker and Deborah M. Hinton 113

Bacterial Responses to Reactive Chlorine SpeciesMichael J. Gray, Wei-Yun Wholey, and Ursula Jakob 141

It Takes a Village: Ecological and Fitness Impactsof Multipartite MutualismElizabeth A. Hussa and Heidi Goodrich-Blair 161

Electrophysiology of BacteriaAnne H. Delcour 179

Microbial Contributions to Phosphorus Cycling in Eutrophic Lakesand WastewaterKatherine D. McMahon and Emily K. Read 199

Structure and Operation of Bacterial Tripartite PumpsPhilip Hinchliffe, Martyn F. Symmons, Colin Hughes, and Vassilis Koronakis 221

Plasmodium Nesting: Remaking the Erythrocyte from the Inside OutJustin A. Boddey and Alan F. Cowman 243

vi

Ann

u. R

ev. M

icro

biol

. 201

3.67

:477

-498

. Dow

nloa

ded

from

ww

w.an

nual

revi

ews.o

rgby

Uni

vers

idad

e Fe

dera

l de

Toca

ntin

s on

01/1

6/14

. For

per

sona

l use

onl

y.

MI67-FrontMatter ARI 12 August 2013 12:26

The Algal Past and Parasite Present of the ApicoplastGiel G. van Dooren and Boris Striepen 271

Hypoxia and Gene Expression in Eukaryotic MicrobesGeraldine Butler 291

Wall Teichoic Acids of Gram-Positive BacteriaStephanie Brown, John P. Santa Maria Jr., and Suzanne Walker 313

Archaeal Biolms: The Great UnexploredAlvaro Orell, Sabrina Frols, and Sonja-Verena Albers 337

An Inquiry into the Molecular Basis of HSV Latency and ReactivationBernard Roizman and Richard J. Whitley 355

Molecular Bacteria-Fungi Interactions: Effects on Environment, Food,and MedicineKirstin Scherlach, Katharina Grau

capit. plant cell wall deconstruction

Documents