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12 Biology, Genetic Aspects, andOxidative Stress Response ofStreptomyces and Strategies forBioremediation of Toxic Metals

Anindita Mitra

Faculty of Arts and Science (FAS), Harvard University, Cambridge, MA02138, USA

12.1 Introduction

Solving environmental problems like toxic metal removal is an important societal

issue. Bioremediation is a sustainable solution for this purpose. Because environmen-

tal systems are more complex and diverse than well-controlled laboratory conditions,

the applications of biology, genetics, and oxidative stress responses of a potential

microorganism offer a promising approach to understand the molecular mechanisms

of bioremediation. The functional genomics provide an insight into global metabolic

and regulatory networks that can enhance the understanding of gene functions and

further pave the way for environmental microbiologists toward a better understand-

ing of microbial bioremediation. To develop an efficient bioremediation strategy

for toxic metals, one has to understand the physiology of the microorganisms in the

contaminated environment, the physio-chemical nature of the contaminated sites

(e.g., oxidation�reduction potential) and the conditions where the functional genes

will be mostly expressed. Where the whole genome annotation is helpful to find the

biodegrading gene/s for a specific metal, the transcriptomics provide us the informa-

tion of a complete set of RNA (transcriptome) produced in one or a population of

cells. Transcriptome reveals the genes that are actively expressed at any given time

under specific set of conditions, thus it varies with external environmental condi-

tions. The progress of molecular biology, system biology, and the availability of

whole genome sequence data, and the techniques like genomics, transcriptomics,

proteomics, and metabolomics, are potentially helpful to understand the microbial

and the field based bioremediation processes (Ma and Zhai, 2012).

Bioremediation works by transforming or degrading the toxic and hazardous

product into less toxic chemicals. Microorganisms cannot degrade metals, but they

can interact with and bio-transform them into another chemical/s by changing their

Microbial Biodegradation and Bioremediation. DOI: http://dx.doi.org/10.1016/B978-0-12-800021-2.00012-1

© 2014 Elsevier Inc. All rights reserved.

http://dx.doi.org/10.1016/B978-0-12-800021-2.00012-1

oxidation state, either by adding or removing electrons. Additionally, the potential

bacteria for remediation must continuously deal with stress situations in vivo. Such

stress conditions may include changes in environmental temperature, pH, humidity,

etc. along with oxidative stress induced by metal-mediated free radicals.

Metals are considered toxic at high concentrations, since they disrupt cell

homeostasis by binding to enzymes, proteins, and DNA and for the production of

oxygen radicals through the Fenton reaction (Schmidt et al., 2007). Therefore, to

maintain a homeostasis within the cell, the potential microbes excrete metals via

efflux transport systems, bind and detoxify metals inside the cells by sequestering

compounds in cytosol, release chelators to bind metals, or bind metals in cell walls

by sorption (Haferburg and Kothe, 2007).

In this respect, Streptomyces spp. has played some advantageous roles over other

microorganisms for multiple reasons, which are discussed in detail here. The purpose

of this review is to provide a detailed overview of the current state of knowledge of

the role of Streptomyces, and its biology and genetics, for the purpose of toxic metals

bioremediation. The chapter is organized in the following manner: First, the advanta-

geous role of Streptomyces over other bacteria is mentioned in general, and then its

genome-scale oxidative stress regulatory networks are discussed. Attention is paid to

the genetic role of Streptomyces spp. for metal-specific regulatory systems and the

possible mechanisms of bioremediation. Finally, we discuss how this knowledge can

be used as a strategy plan for a metal bioremediation process.

12.2 Genus Streptomyces

Streptomyces is one of the largest genus of Actinobacteria. This Gram-positive

soil-dwelling bacteria has three characteristic developmental phases: (1) formation

of branched, filamentous vegetative mycelium, (2) formation of aerial hyphae, and

(3) the production of spores. The cell wall of Streptomyces contains peptidoglycan

and teichoic acids, which are considered the major metal-binding sites (Beveridge

and Murray, 1980). The active secondary metabolisms of Streptomyces spp. also

facilitate multiple metal-binding sites. Even some secondary metabolic products

help the bacteria to cope with stressful environments including heavy-metal-

contaminated sites (So et al., 2000).

Streptomyces strains resistant to metals are not confined to a single lineage but

are widespread along Streptomyces phylogeny (Alvarez et al., 2013). It has a large

linear chromosome with high G1C content (about 70%), which gives much stabil-

ity. Interestingly, the genes associated with metal resistance are not only confined to

the chromosome but also spread over the plasmids (Ravel et al., 1998), and thus the

presence of metal resistance can be found due to the transfer of plasmids with metal

resistance genes (Alvarez et al., 2013). The exchange of genetic materials and gene

duplications are widespread across Streptomyces species (Zhou et al., 2012).

Further, the complete genome sequences of five Streptomyces species and, addition-

ally, the numerous sequence isolates of different Streptomyces species from diverse

288 Microbial Biodegradation and Bioremediation

environments have strengthened the scope for using this genus for bioremediation

purposes. Analysis of the “core genome” components of Streptomyces revealed that

it contains a substantial percentage of catalytic activity, transferase activity, hydro-

lase activity, and metabolic processes involving genes, along with a strong oxidative

stress regulatory network and metal-detoxifying network (Zhou et al., 2012). Where

the “core genome” of Streptomyces holds most of the housekeeping genes, the

“arms” of the genome consist mostly of the conditional adaptive genes, which are

probably generated by lateral gene transfer and gene duplication (Hopwood, 2007).

12.3 Oxidative Stress Regulation and Metal Detoxification

Metal-contaminated sites may impose oxidative stress on the inhabitant bacteria.

This oxidative stress is mainly generated due to the metal-mediated reactive oxygen

species (ROS), including free radicals, oxides, and peroxide that may cause various

modifications to DNA bases, lipid peroxidation, and altered calcium and sulfhydryl

homeostasis. To survive in the metal-contaminated environment, the microorgan-

ism has to defend against oxidative stress via its native regulatory pathways and

detoxify ROS or repair the resulting damages. In Streptomyces, the intracellular

binding and detoxification of metal species are combined with oxidative stress

defense mechanisms (Figure 12.1).

In general, iron (Fe), copper (Cu), chromium (Cr), vanadium (V), and cobalt

(Co) undergo redox-cycling reactions, while for mercury (Hg), cadmium (Cd), and

nickel (Ni), the primary route to interact with living cells is by depletion of gluta-

thione or superoxide dismutase and bonding to sulfhydryl groups of proteins

(Valko et al., 2005). The common mechanisms for iron, copper, chromium, vana-

dium, and cobalt involve Fenton reactions, and generation of superoxide radicals

and hydroxyl radicals in mitochondria, microsomes, and peroxisomes (Valko et al.,

2005). Streptomyces species exhibit different tolerance sensitivity to different

metals (Abbas and Edwards, 1989). Working with 32 Streptomyces species, Abbas

and Edwards (1989) found that these sensitivities toward metals are in order of tox-

icity: Hg.Cd.Co.Zn.Ni.Cu.Cr.Mn.

In order to prevent damage, Streptomyces has developed a number of enzymatic

and nonenzymatic protection systems along with repair and detoxification pro-

cesses. The enzymes named catalase-peroxidase and superoxide dismutase are

widely known to detoxify intercellular ROS. It was observed that the metabolic

pathways lead to precipitate metals as metal sulfides; phosphates or carbonates

have a significant possible biotechnological application.

12.3.1 Thiol Systems

12.3.1.1 Thioredoxin System

In Streptomyces, the thiol-disulfide status of proteins is maintained by a thioredoxin

system. This is one of the most important antioxidant systems in Streptomyces to

289Biology, Genetic Aspects, and Oxidative Stress Response

protect against oxidative stress and to maintain intracellular thiol homeostasis.

The system is composed of small redox-active proteins, thioredoxin (TrxA), and thior-

edoxin reductase (TrxB). The reduced thiol state of thioredoxins is maintained by

thioredoxin reductase by transferring electrons from NADPH to two cysteine residues

in the TrxB active site that, in turn, can reduce oxidised TrxA (Hengst and Buttner,

2008). The thioredoxin systems have been studied in several Streptomyces strains like

Streptomyces aureofaciens (Horecka et al., 2003) and Streptomyces coelicolor

(Stefankova et al., 2006). The model organism, S. coelicolor, consists of many thiore-

doxins (encoded by SCO3890, SCO3889, SCO5438, SCO5419, and trxC/SCO0885)

(Paget et al., 2001a).

12.3.1.2 Mycothiol System

Another important thiol system in Streptomyces is mycothiol (MSH), which exists

in reduced (MSH) and oxidized dimeric mycothiol disulfide (MSSM) states.

Mycothiol is highly resistant to oxidation by metal-derived molecular oxygen, even

much more resistant than cysteine or glutathione. In order to maintain the

Fe3+ Fe3+

Fe3+

Fe3+

Fe3+

Co2+

Co2+

Co2+

Ni2+

Ni2+

Zn2+

Zn2+

Metal-contaminated sites

Oxidative stress-responsive genes

Regulatory systems

OxyR

OhrR

Rex

σR–RsrA

Metal-responsive genesFurS

CatR

Nur

ZurThioredoxin

Mycothiol

Fur and Fur homologous

Inside the Streptomyces cells

Wbl

Iron–sulfur cluster

Mn2+

Mn2+Mn2+

Zn2+

Figure 12.1 Schematic figure of the genes involved in regulation of metal homeostasis and

oxidative stress in Streptomyces spp. in the metal-contaminated sites.

Source: Modified from Zhang et al. (2013).


intracellular redox environment, an NADPH-dependent flavoenzyme named

mycothiol-disulfide-selectivereductase (Mtr) reduces MSSM back to MSH (Hengst

and Buttner, 2008). In S. coelicolor, MSH is under the control of sigma(R), which

is regulated by a redox- sensing anti-sigma, factor, RsrA with a thiol-disulfide

redox switch (discussed later). MSH can reduce RsrA to bind sigma(R), so that the

RsrA-sigma(R) system senses the intracellular level of reduced MSH, and MSH

serves as a natural modulator of the transcription system (Park and Roe, 2008).

12.3.2 Iron�Sulfur Clusters

Iron�sulfur [Fe�S] clusters exist as [2Fe�2S], [4Fe�4S], [3Fe�4S], or more

complex forms, depending upon the cell’s redox status, and controls the activities

of transcriptional regulations involved in oxidative stress. These clusters of proteins

are involved in electron transport and metabolic pathways across all live kingdom

(Jakimowicz et al., 2005). Three transcription factors, Fumarate and Nitrate reduc-

tase Regulator (FNR), Super oxide response Regulator (SoxR), and Iron-sulphur

cluster Regulator (IscR), are identified in Streptomyces that have Fe�S regulatory

clusters. FNR regulates the expression of a number of genes involved in anaerobic

respiration. In Streptomyces lividans, IscS-like cysteine desulfurase-DndA, which is

required for the formation of an [Fe�S] cluster in apo-DndC, was identified (Chen

et al., 2012). The [2Fe�2S] cluster of SoxR senses superoxide and NO stresses

(Sheplock et al., 2013). SoxR, then activates other genes to remove superoxide and

repair the damage that may have occurred during oxidative stress.

In S. coelicolor, five SoxR regulon genes (SCO2478, -4266, -7008, -1909,

and -1178) were identified (Shin et al., 2011).

12.3.3 The Wbl Proteins

The wbl genes found in the entire Streptomyces genera play an important role in its

biology. Its four cysteine residues, which are conserved in all members, might act as

ligands for metal cofactor (Jakimowicz et al., 2005). The WhiD, a developmental

protein in Streptomyces and a member of the WhiB-like (Wbl) family, can bind a

redox-sensitive [4Fe�4S] cluster that reacts with oxygen to generate a [2Fe�2S]

cluster. This WhiD is required for the late stages of sporulation in S. coelicolor

(Jakimowicz et al., 2005). Genome sequencing of S. coelicolor revealed that, includ-

ing whiB and whiD, there are a total of 14 wbl genes: 11 on the chromosome and

3 on the giant linear plasmid, SCP1 (Bentley et al., 2002; Bentley et al., 2004).

However, Wbl may function as disulfide reductase, where the [4Fe�4S] cluster

inactivates the enzyme until oxidative stress destroys the cluster and the enzymatic

activity is released (Hengst and Buttner, 2008).

12.3.4 Fur and Fur Homologous

In Streptomyces, the Ferric Uptake Repressor (Fur)-like proteins regulate catalase-

peroxidase (CpeB) and act as redox regulators. While catalases decompose


hydrogen peroxide to water and oxygen, peroxidases use hydrogen peroxide to oxi-

dize a number of compounds. Thus, functional catalase-peroxidases are composed

of varying ratios of these two enzymatic activities. Though initially, Fur was char-

acterized as an iron-responsive regulator, it was later revealed that in addition to

iron, different Fur homologous can act as metal sensors of (Zn21, Ni21, Mn21 and

Co21 (Santos et al., 2008). There are four members in the Fur family: FurS and

CatR are redox-responsive regulators that control the expression of antioxidant

genes, and Zur and Nur control zinc and nickel homeostasis in cell, respectively.

12.3.4.1 FurS

FurS is a zinc-containing redox regulator that regulates cpeB gene in Streptomyces

reticuli in its thiol-reduced (SH) form by binding in a furS-cpeB operon (Lucana and

Schrempf, 2000). Under oxidative stress conditions, the oxidized SH group of FurS is

unable to block the transcription of furS-cpeB, which in turn leads to a high production

of catalase peroxidase (CpeB) activity (Lucana et al., 2003). Another catalase-peroxi-

dase�encoding furS-cpeB operon was isolated from S. coelicolor (Hahn et al.,

2000a). FurA, a metal-dependent repressor, acts as a negative regulator of the

furS-cpeB operon. The binding affinity of FurA is increased in the presence of metals

and under reducing conditions, and thus decreases the production of CatC protein.

12.3.4.2 CatR

S. coelicolor produces three distinct catalases: two monofunctional catalases (CatA

and CatB) and one catalase-peroxidase (CatC). CatA is induced by H2O2, and is

required for efficient growth of mycelium, whereas CatB is induced by osmotic

stress and is required for osmo-protection of the cell. CatC is transiently expressed

at the late exponential to early stationary phase, but its function has not been well

documented (Hahn et al., 2000b).

12.3.4.3 Nur

A nickel-responsive regulator of the Fur family named Nur, regulates superoxide

dismutases (SODs) in Streptomyces spp. (Ahn et al., 2006). The SODs maintain the

concentration of superoxide radicals in low limits through the catalysis of the dismu-

tation of superoxide (O22 ) into oxygen and hydrogen peroxide. The SODs are named

according to the metal species attached to the redox-active site. However, the pres-

ence of cytoplasmic nickel-dependent SOD (NiSOD) is a general feature of the

Streptomyces (Leclere et al., 1999) genus. This novel type of SOD with only nickel

as the catalytic metal was first identified and characterized by Youn et al. (1996).

S. coelicolor contains two types of SODs, Ni containing SodN and Fe� containing

SodF and SodF2 (Chung et al., 1999). Nur binds to the promoter region of the

sodF and sodF2 genes encoding Fe-containing SOD in the presence of nickel (Ahn

et al., 2006).

Later, from the Streptomyces peucetius ATCC 27952 genome, two SODs,

named sp-sod1 and sp-sod2, were identified and characterized. The sp-sod1 is an


Fe�Zn sod, while sp-sod2 is a NiSOD; they are 636 and 396 bp in length, respec-

tively (Kanth et al., 2010). The heavy metal (Ni, Cu, Cd, Cr, Mn, Zn, Fe)�tolerant

strain Streptomyces acidiscabies E13 isolated from a uranium mining site also

showed the presence of Ni and Fe� containing superoxide dismutase in different

enzymatic repression studies (Schmidt et al., 2007).

12.3.4.4 Zur

Zur is a zinc-specific regulator of the Fur family that regulates zinc transport and

maintains zinc homeostasis in the cell. Zur regulates Zn mobilization with some

ribosomal proteins (S14, S18, L28, L31, L32, L33, and L36) (Owen et al., 2007).

The proteins, those are predicted with Zn ribbon motifs consist of two pairs of

conserved cysteine residues are named C1, that in turn bind Zn. The other proteins

are C2, as they lack cysteine containing Zn ligands. In S. coelicolor, the expression

of four transcription units encoding C2 ribosomal proteins is elevated under condi-

tions of zinc deprivation (Owen et al., 2007). Among these four transcriptional

units, Zur controls only three; the fourth one, rpmG3� rpmJ2, is not controlled by

Zur. In S. coelicolor, the rpmG3� rpmJ2 is influenced by σR�RsrA redox switch,

that also controls the disulfide stress condition. Depletion of zinc in S. coelicolor

cultures leads to the release of σR from the σR�RsrA complex (Owen et al., 2007;

Shin et al., 2007). Zur also regulates the zinc transport system through the znuACB

operon (Owen et al., 2007). A putative zincophore named Coelibactin, regulated by

Zur, is reported in S. coelicolor (Hesketh et al., 2009; Kallifidas et al., 2010).

Later, a crystal structure of active Zur with three zinc binding sites (C-, M-, and D-

sites) is reported from S. coelicolor (Shin et al., 2011). Biochemical and spectro-

scopic analyses revealed that while the C-site serves a structural role, the M- and

D-sites regulate DNA-binding activity as an on-off switch and a fine-tuner, respec-

tively (Shin et al., 2011).

12.3.5 The Regulatory Systems

12.3.5.1 OxyR

OxyR is a H2O2-sensing transcriptional regulator. In S. coelicolor, OxyR regulates

the expression of its own structural gene and the alkyl hydroperoxide reductase sys-

tem (AhpC and AhpD). In presence of H2O2, OxyR influences oxyR and ahpCD

promoters as a positive regulator (Hahn et al., 2002). However, the mechanism by

which OxyR senses peroxides is still controversial.

12.3.5.2 OhrR

Under oxidative stress conditions, lipid hydroperoxide, a nonradical product

promotes further formation of reactive lipid radicals and oxidized macromolecules

that has an adverse effect on membrane components (Oh et al., 2007). The organic

hydroperoxide resistance (Ohr) enzymes reduces peroxides generated from lipid per-

oxidation in a thiol-dependent manner. The OhrR acts as an organic peroxide-sensing


transcriptional repressor of ohr gene. Out of three paralogous ohr genes (ohrA, ohrB,

and ohrC) found in S. coelicolor, only the expression of ohrA is induced by organic

hydroperoxides and provides primary protection against organic hydroperoxides. In

reducing conditions, OhrR represses the ohrA and ohrR genes. The oxidization by

organic hydroperoxides causes de-repression of the ohrA gene, and the ohrR gene is

induced through activation by OhrR (Oh et al., 2007).

12.3.5.3 Rex

The redox- sensing transcriptional repressor (Rex) homologues act as regulatory

sensors of NADH/NAD1 in most Gram-positive bacteria, including Streptomyces.

The NADH/NAD1 turnover in the cell is highly influenced by oxygen. Rex is a

repressor that controls expression of the cytochrome bd terminal oxidase operon

(cydABCD), which has a high affinity for oxygen and also controls its own tran-

scription as part of the rex�hemACD operon. Rex binds both NADH and NAD1,

but high affinity of Rex to NADH outcompetes NAD1. Thus, the cellular NADH/

NAD1 ratio allows Rex to repress target genes by binding to their respective Rex

operator (ROP) sites and thus influence the electron transport chain (Brekasis and

Paget, 2003).

12.3.5.4 σR�RsrA

It senses and responds to disulfide stress. In a reducing environment, σR is seques-

tered by RsrA and form 1:1 complex that prevents σR from interacting with RNA

polymerase. But in disulfide stress, an intramolecular disulfide bond is formed in

RsrA that results the removal of Zn21 and loss of σR binding. The resultant free σR

then binds to RNA polymerase and activates the target genes (Paget et al., 2001b).

In contrast, the induced thioredoxin, in turn, reduces RsrA, which forms a negative

feedback loop. It allows intracellular redox homeostatic control by RsrA.

12.3.6 Other Metal Resistance in Streptomyces

Genome sequencing of Streptomyces xinghaiensis NRRL B24674T revealed a num-

ber of genes related to the heavy metal resistance of mercury, copper, and nickel,

indicating a potentiality of the strain for environmental bioremediation (Zhao and

Yang, 2011). In heavy metal-resistant Streptomyces acidiscabies, a highly specific

nickel transporter gene was found (Amoroso et al., 2000) that was also identified in

the genome of Streptomyces avermitilis.

During early genetic characterization of S. lividans, an amplifiable sequence

named AUD2, linked to the mer genes, was isolated from SLP3 plasmid (Cruz-

Morales et al., 2013). After transcriptional analysis of S. lividans 66, a large genome

island was identified that is rich in metal-related genes (Cruz-Morales et al., 2013).

A strong correlation was observed between production of melanin and metal

resistance for phytopathogenic Streptomyces scabies (Beausejour and Beaulieu,


2004). Melanin can reduce the concentration of ROS and can sequestrate metals.

This may be due to the presence of carboxylic groups in the melanin molecule.

It has been reported that Streptomycete species are able to detoxify Hg12 to

volatile Hg0 by using mercuric reductase enzyme (Abbas and Edwards, 1989).

Many genes are predicted for the resistance to metals and metalloids from the draft

genome of Streptomyces zinciresistens K42, isolated from copper�zinc mine

(Lin et al., 2011). The soil-borne Streptomyces tendae F4, produces three different

hydroxamate siderophores, that reduces cadmium toxicity and increases metal

uptake (Dimkpa et al., 2009).

12.4 Metal Detoxification Mechanisms and Bioremediation

Microbes can influence metals (Ledin, 2000; Barkay and Schaefer, 2001) by increas-

ing the mobility of the contaminants or they can transform metals to precipitate out

from the contaminated site. However, these mechanisms can be utilized for potential

bioremediation purposes only once the microbial metabolisms, chemical reactions,

and flow of metal contaminants in the environment are well understood. In

Figure 12.2, the possible mechanisms for metal bioremediation by Streptomyces and

its involved genes are summarized. Using these mechanisms, Streptomyces can (a)

transform metals by redox or alkylation processes; (b) accumulate metals by

Oxidized metal(Fe(III), Cr(VI) U(VI))

Reduced metal(Fe(II), Cr(III) U(IV))

BiotansformationExtracellular complexation

(e.g. siderophores forming gene)

Efflux

Enzymatic detoxification(e.g., nickel superoxide dismutase)

Inside the Streptomyces Cells

Intracellular precipitation Metal chelation(e.g., metallothionein)

Secondary metabolitesbinds/mobilize metals

Volatilization(e.g., mercuric reductase) Biotransformation

Oxidized metal(Fe(III))

Reduced metal(Fe(II))Hg0 Hg+2

Figure 12.2 Schematic of the possible mechanisms of metal bioremediation in Streptomyces

spp. and the involved genes.

Source: Modified from Gadd (2010).


absorption or adsorption processes. In addition, (c) the organic substances produced

or released from the microorganism sometime may influence the mobility of the

metals or bind the metals, (d) even microbes can influence metal mobility indirectly

by changing pH and Eh of the contaminated site, and lastly, (e) organic�metal com-

plexes degraded by microbes may alter metal specition. In order to acquire iron from

the extracellular environment, Streptomyces produces and secretes low-molecular-

weight compounds known as siderophores. These compounds chelate Fe31.

In Streptomyces pilosusis, iron uptake is mediated by ferrioxamines B, D1, D2, and

E, while the iron transport is maintained by exogenous siderophores ferrichrome,

ferrichrysin, rhodotorulic acid (RA), and synthetic enantio-RA (Muller et al., 1984).

Under iron-rich conditions in a cell, Fur binds the divalent iron and inhibits DNA tran-

scription from the genes and operons repressed by the metal. Conversely, when iron

is scarce, there is de-repression of the genes that activate other iron uptake systems.

In S. coelicolor A3(2), des and cch gene clusters are identified that direct the produc-

tion of siderophores, named tris-hydroxamate ferric iron-chelators desferrioxamine E

and coelichelin, respectively (Barona-Gomez et al., 2006).

12.5 Strategies, Applications, and Future Direction

The potential of microorganisms for the sustainable bioremediation of toxic metals

is well established. Bioremediation strategies depend solely upon the catabolic

capacities of the microbes to transform toxic metals to harmless compounds.

However, there is a substantial difference between manipulated laboratory condi-

tions and the natural environment. It is also not surprising that the genetically mod-

ified bacteria rarely function in the in situ environment.

Microbes have evolved for the last 3.8 billion years and inhabit virtually all envir-

onments, from extreme salinity and extreme pH to extreme temperature. Thus, it is

important to know about their metabolic capabilities by analyzing the target gene and

its potentiality before using it in the target niche. Earlier strategies to discover the

potential strains were based solely on the lab-based experimental data of microbe’s

chemical kinetics, and on intermediate and final product identification and quantifica-

tion of the metal pollutants. Now, with the advancement of genomics, it has been eas-

ier to find the specific gene responsible for a specific metal bioremediation purpose

before proceeding to on-site evaluation. Selection of microbes for bioremediation

purpose should be based on its functional genomics that can shed light on the under-

standing of the biological functions of specific sets of genes and how genes and their

products work together (Zhao and Poh, 2008); and transcriptomic study that will

determine when and where the genes are turned on or off in various environmental

situations. Strategies for microbial bioremedation based on the understanding of the

molecular mechanisms will reduce uncertainty about the functional capability of the

strain in field applications. Thus, the integration of transcriptomics, proteomics, and

functional genomics provide us the global metabolic and regulatory gene networks


that can enhance the understanding of gene functions. This strategy will give a pow-

erful new perspective on the holistic use of Streptomyces for metal bioremediation.

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