review article microbial degradation of indole and...

Review ArticleMicrobial Degradation of Indole and Its Derivatives

Pankaj Kumar Arora1 Ashutosh Sharma2 and Hanhong Bae1

1School of Biotechnology Yeungnam University Gyeongsan 712-749 Republic of Korea2Escuela de Ingenieria en Alimentos Biotecnologia y Agronomia Instituto Tecnologico y de Estudios Superiores de MonterreyEpigmenio Gonzalez 500 Colonia San Pablo QRO Mexico

Correspondence should be addressed to Pankaj Kumar Arora arora484gmailcom and Hanhong Bae hanhongbaeynuackr

Received 4 February 2015 Revised 19 March 2015 Accepted 19 March 2015

Academic Editor Qing X Li

Copyright copy 2015 Pankaj Kumar Arora et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Indole and its derivatives including 3-methylindole and 4-chloroindole are environmental pollutants that are present worldwideMicrobial degradation of indole and its derivatives can occur in several aerobic and anaerobic pathways these pathways involvedifferent known and characterized genes In thisminireview we summarize and explain themicrobial degradation of indole indole-3-acetic acid 4-chloroindole and methylindole

1 Introduction

Indole and its derivatives comprise a major group of hete-rocyclic aromatic compounds which are widely used for thesynthesis of pharmaceuticals dyes and industrial solvents[1] Indole is used as a perfume fixative a synthetic flavorand a chemical intermediate for synthesis of a plant growthregulator indole-3-acetic acid [1 2] 2-Methylindole is usedfor dye manufacturing including cyanine dyes and cationicdiazo dyes [3] The indole ring is also present as a core build-ing block and key functional group inmany pharmaceuticalsalkaloids and hormones [4]

Indole and its derivatives are also present inmany naturalproducts indole occurs naturally in Robinia pseudoacaciathe jasmines certain citrus plants and the wood of Celtisreticulata [1] Indole is also present in coal tar [5] fuel oil [6]and cigarette smoke [7 8] Indole is one of the main degrada-tion products of microbial metabolism of L-tryptophan anessential amino acid present in most proteins [9 10] Morethan 85 species of Gram-positive andGram-negative bacteriacan produce indole [11] 3-Methylindole is commonly foundin feces and sewage and is well known for its unpleasant smell[1 12ndash14] Indole-3-acetic acid (auxin) is a naturally occurringplant hormone that has a significant role in plant growth anddevelopment

Indole and its derivatives are discharged into the environ-ment through industrial waste coal tar waste andwastewaterfrom coking plants coal gasification [5 15 16] and refineries[6] and cigarette smoke

Human beings can be exposed to indole via (i) ambientair (ii) tobacco smoke (iii) food and (iv) skin contact withvapors and other products such as perfumes that containindole

Indole and its derivatives are highly toxic to microor-ganisms and animals and are considered mutagens andcarcinogens [17 18] Experimental evidences showed thatindole caused glomerular sclerosis [19] hemolysis [20ndash22]improper oviduct functioning [23] and chronic arthritis [2425] Indole inhibits anthraquinone biosynthesis in plants [26]Furukawa et al [27] reported that a derivative of indole-3-acetic acid induced neuroepithelial cell apoptosis in ratembryos

4-Chloroindole irritates the eyes skin lungs and respir-atory system and shows antimicrobial activity against sev-eral Gram-positive and Gram-negative bacteria [28 29]Nitrosated 4-chloroindole and 4-chloro-6-methoxyindoleare genotoxic specifically they induced sister chromatidexchanges in Salmonella typhimurium TA100 [30] 3-Methy-lindole causes malabsorption syndrome anemia and hepaticcoma in human beings [31] Furthermore 6-hydroxyskatol

Hindawi Publishing CorporationJournal of ChemistryVolume 2015 Article ID 129159 13 pageshttpdxdoiorg1011552015129159

2 Journal of Chemistry

a metabolite of 3-methylindole generated in the humanintestine has possible psychotropic effects [31]

Indole and its derivatives are considered environmentalpollutants due to their toxicity and worldwide occurrencein soils coastal areas groundwater surface waters and evenindoor environments [15 32] Several reviews are availablefor applications andmicrobial production of indole howeverthere are very few reviews onmicrobial degradation of indole[4 11] Recently rapid progress was made in the study ofmicrobial degradation of indole and its derivatives and a fewnew pathways were proposed for microbial degradation ofindole and its derivatives [28 33 34] The aim of this reviewis to summarize the microbial degradation of indole indole-3-acetate 4-chloroindole and methylindole and highlightrecent developments in the field

2 Microbial Degradation of Indole

Microbial degradation of indole was investigated underaerobic and anaerobic conditions [12 13 15 33 34] Severalmechanisms were proposed for indole biodegradation bymicroorganisms including bacteria and fungi under aerobicconditions [12 35ndash37 46] microorganisms either mineral-ized indole completely [36 37 46] or transformed it intoother compounds in the presence of an additional carbonsource (cometabolism) [33 34] Under aerobic conditionsindole metabolism was generally initiated by oxidation ofindole followed by heterocyclic ring cleavage

21 Bacterial Mineralization of Indole A few indole-mineralizing bacteria have been isolated and characterizedfor aerobic biodegradation of indole [35ndash37 46]Threemajorpathways for indole mineralization have been proposed andthese pathways are the catechol pathway the gentisatepathway and the anthranilate pathwayThe catechol pathwaywas studied in an indole-mineralizing Gram-negativebacterium isolated from tap water [35] The first step of thecatechol pathway was hydroxylation of indole to indoxylwhich was further hydroxylated to 23-dihydroxyindole(Figure 1(a)) Further degradation proceeded via isatinN-formylanthranilic acid anthranilic acid salicylic acid andcatechol [35]The anthranilate pathway of indole degradationwas studied in a Gram-positive coccus that utilized indoleas its sole source of carbon and energy and degraded itvia 23-dihydroxyindole N-carboxyanthranilic acid andanthranilic acid (Figure 1(b)) [36] Claus and Kutzner [37]reported the gentisate pathway of indole degradation in anindole-mineralizing bacterium Alcaligenes sp In 3 isolatesfrom activated sludge In this pathway indole degradationoccurred via indoxyl isatin anthranilic acid and gentisicacid (Figure 1(c)) the formation of gentisic acid was a keyfeature of this pathway formed due to hydroxylation ofanthranilic acid The possibility of new indole degradationpathways aside from these 3 isolates has been suggestedDoukyu and Aono [46] reported the mineralization ofindole via isatin and isatic acid in Pseudomonas sp strainST-200 Yin et al [47] studied indole degradation in anindole-mineralizing bacterium Pseudomonas aeruginosaGs isolated from mangrove sediments and detected two

major metabolites however they could not identify eithermetabolite

22 Bacterial Cometabolism of Indole Cometabolism ofindole involves bacterial transformation of indole into othercompounds in the presence of additional carbon sourceThese biotransformed products may belong to one or moredegradation pathways of indole Fukuoka et al [34] studiedthe biotransformation of indole in Cupriavidus sp strainKK10 isolated from a soil bacterium consortium andproposed multiple pathways for indole biotransformationbased on the identified metabolites These pathways involveoxidation of indole followed by either N-heterocyclic ringcleavage or carbocyclic aromatic ring cleavage (Figure 2)In the carbocyclic aromatic ring cleavage pathway indolewas oxidized at the 4th and 5th positions to form 45-dihydroxyindole via cis-45-indole-dihydrodiol [34]The 45-dihydroxyindole underwent ortho- and meta-ring cleavageThe meta-ring cleavage product was identified as 4-(3-hydroxy-1H-pyrrol-2-yl)-2-oxo-but-3-enoic acid whereas 3-(2)-formyl-1H-pyrrole-2-(3)-carboxylic acid was identifiedas the ortho-ring cleavage product which was furthercarboxylated to pyrrole-23-dicarboxylic acid [34] The N-heterocyclic aromatic ring cleavage pathway followed oneof the following two mechanisms (i) monooxygenation ofindole at the 2 or 3 positions to form a corresponding indoxylthat further converted to a corresponding oxindole whichwas further transformed to isatin or (ii) dioxygenation ofindole at the 2 and 3 positions to form 23-dihydroxyindolevia indole-23-dihydrodiol [34] In the next step the isatinor 23-dihydroxyindole underwent N-heterocyclic ortho-ringcleavage to produce N-formylanthranilic acid which wasconverted to anthranilic acid Anthranilic acid was deami-nated to produce salicylic acid which was transformed togentisic acid via monohydroxylation The gentisic acid wasconverted to 124-trihydroxybenzene which could furtherproduce TCA cycle intermediates [34] The novel feature ofthis pathway is the previously unreported formation of 124-trihydroxybenzene Indigoids such as indigo indirubinisoindigo and 22-bis(31015840-indolyl) indoxyl were also biotrans-formation products of indole in Cupriavidus sp KK10 [34]

Another biotransformation pathway of indole was inves-tigated in Arthrobacter sp SPG Initially indole was bio-transformed into indole-3-acetic acid via a tryptophan-independent pathway [33] Indole-3-acetic acid was con-verted to indole-3-glyoxylic acid which was converted toindole-3-aldehyde (Figure 3(a)) Kim et al [48] reported thata plant polyphenol stimulated indole biotransformation inBurkholderia unamae CK43B isolated from the polyphenol-rich Shorea rhizosphere Polyphenol-exposed cells of strainCK43B utilized indole as a nitrogen source and degraded itvia anthranilic acid and catechol [48]

Indole can be biologically oxidized to indoxyl and thenindoxyl is spontaneously transformed to a dimer indigo(Figure 3(b)) a blue pigment [49 50]Manymicroorganismsinvolved in the transformation of indole into indigo havebeen isolated and characterized [49 50] including naph-thalene-degrading Pseudomonas putida PgG7 [51] m- andp-toluate-degrading P putida mt-2 [52] toluene-degrading

Journal of Chemistry 3

NH

NH

OH

NH

OH

OH

NH

O

O

COOH

NHCHO

COOH

COOH

OH

OH

OH

NH

OH

OH

COOH

NHCOOH

NH

OH

NH

O

O

COOH

COOH

OH

OH

COOH

IndoleIndoxyl Indoxyl

23-Dihydroxyindole

Isatin

N-Formylanthranilic acid

Anthranilic acid

Salicylic acid

Catechol

23-Dihydroxyindole

N-Carboxyanthranilic acid

Anthranilic acid

Anthranilic acid

Isatin

Gentisic acid

(a)

(b)

(c)

NH2

NH2

NH2

Figure 1 Metabolic pathways for mineralization of indole in (a) tap water bacterium [35] and (b) a gram positive coccus [36] and (c) anAlcaligenes sp In 3 [37]


NHN

H

OH

HOH

H

NH

OH

HO

HOOC

NHHOOC OHC

HOOC

NH

HOOC

HOOC

NH

HOOC

NH

HOOC

O

NH

OH

OH

H

H

NH

OH

OHCOOH

NH

OH

NH

OH

NH

O

NH

O

NH

O

O

OH

COOH

OH

COOH

HO

OH

OH

HO

TCA

Carbocyclic aromatic ring cleavage pathway

N-Heterocyclic ring cleavage pathway

Indole

3-Indoxyl 2-Indoxyl

3-Oxindole2-Oxindole

Isatin

Indole-23-dihydrodiol

23-DihydroxyindoleAnthranilic acidSalicylic acidGentisic acid

124-Trihydroxybenzene

cis-45-Indole-dihydrodiol 45-Dihydroxyindole 4-(3-Hydroxy-1H-pyrrol-2-yl)-2-oxo-but-3-enoic acid

m-Ring cleavage

O-Ring cleavage

Pyrrole-23-dicarboxylic acid 3-(2)-Formyl-1H-pyrrole-2-(3)-carboxylic acid

NH2

Figure 2 Degradation pathways of indole in Cupriavidus sp KK10 [34] via carbocyclic ring cleavage and N-heterocyclic ring cleavage

P mendocina KR1 [53] styrene-degrading P putida S12and CA-3 [54] and tetralin-degrading Sphingomonas macro-goltabida [55] Pathak and Madamwar [56] reported thata naphthalene-degrading strain Pseudomonas sp HOB1synthesized indigo and that indigo production increasedwhen naphthalene was used as a growth substrate Mercadalet al [57] optimized the conditions of indigo productionby a naphthalene-degrading marine strain Pseudomonas spJ26 and achieved maximum production of indigo (1381 120583M)using 25mM indole at 25∘C

Several enzymes such asmonooxygenases dioxygenasesand cytochrome P450 were characterized for indigo produc-tion [50] Many genes encoding these enzymes were clonedand used to construct engineering bacteria for efficient indigo

production [50] Ensley et al [51] cloned and expresseda DNA fragment of a Pseudomonas plasmid containingnaphthalene oxidation genes in E coli and observed thatthe recombinant E coli synthesized indigo in nutrient-richmedium indigo production increased in the presence oftryptophan or indole Wu et al [58] transferred a plasmidcontaining naphthalene degrading genes from Pseudomonassp S13 to E coli The recombinant E coli was able to syn-thesize indigo [58] Qu et al [59] showed that E coli thatexpressed biphenyl dioxygenase and biphenyl-23-dihydro-diol-23-dehydrogenase efficiently transformed indole toindigo E coli that expressed cytochrome P450 also oxidizedindole to indigo The immobilization of E coli BL21 express-ing P450 BM-3 showed better rates of indigo production


NH

NH

NH

COCOOH

NH

CHO

Indole Indole-3-acetic acid Indole-3-aldehydeIndole-3-glycoxylic acid

CH2COOH

(a)

NH

NH

OH

NH

ONH

OIndole Indoxyl Indigo

(b)

Figure 3 Biotransformation of indole to indole-3-aldehyde (a) and indoxyl (b)

than nonimmobilized cells [60] The xylA gene that encodesxylene oxygenase was cloned from the TOL plasmid pWW53of P putida MT53 and is responsible for indigo production[61] Nagayama et al [62] constructed a cosmid libraryof metagenomic DNA in E coli and introduced it into Pputida-derived strains that produced little indigo on indole-containing agar plates Screening results showed that 29cosmid clones generated indigo on the indole-containingagar plates [62] Six representative cosmids were selectedfor sequencing and in vitro transposon mutagenesis leadingto the identification of genes encoding putative classes Band D flavo protein monooxygenases a multicomponenthydroxylase and a reductase that were responsible for indigoformation [62]

23 Fungal Degradation of Indole Fungal degradation ofindole has also been investigated [12 38 63] Kamathand Vaidyanathan [12] elucidated a metabolic pathway forindole in Aspergillus niger In this pathway indole was firstoxidized to 3-indoxyl (3-hydroxyindole) that was furtherconverted to N-formylanthranilic acid In the next stepN-formylanthranilic acid was transformed to anthranilicacid by N-formylanthranilate deformylase The anthranilicacid underwent oxidative deamination and hydroxylationcatalyzed byNADPH-dependent anthranilate hydroxylase toproduce 23-dihydroxybenzoic acid that was decarboxylatedto catechol by 23-dihydroxybenzoate decarboxylase (Fig-ure 4(a)) The further degradation of catechol occurred viaring cleavage by catechol-12-dioxygenase

Another fungal metabolic pathway of indole was studiedin an endophytic fungus Phomopsis liquidambari whichutilized indole as its sole source of carbon and nitrogen[38] In this fungus indole was initially oxidized to oxindoleand isatin In the next step isatin was transformed to 2-dioxindole The 2-dioxindole was further converted to 2-aminobenzoic acid via pyridine ring cleavage (Figure 4(b))[38] Katapodis et al [63] reported indole degradation bya thermophilic fungus Sporotrichum thermophile using apersolvent fermentation system containing a large amount ofindole (the medium contained 20 soybean oil by volume

and up to 2 gL indole)They reported that most of the indolewas partitioned in the organic solvent layer and completeindole degradationwas observed after 6 dayswhen the funguswas grown on media containing indole at 1 gL [63]

24 Anaerobic Bacterial Degradation of Indole Anaerobicdegradation of indole has been achieved by pure or mixedculture(s) of bacteria under denitrifying sulfate-reducingor methanogenic conditions [64ndash71] Mixed microbial pop-ulations present in marine sediments [64 65] freshwatersediments [64 66 67] sewage sludge [68ndash70] and com-posting pig and chicken manure [13] could anaerobicallydegrade indole Wang et al [71] reported mineralization ofindole into carbon dioxide and methane by a consortium ofmethanogenic bacteria Berry et al [72] reported conversionof indole to oxindole under methanogenic conditions Mad-sen et al [66] investigated the effects of physiological andenvironmental factors on the accumulation of oxindole dur-ing anaerobic indole degradation and reported that oxindolewas accumulated under methanogenic conditions but notunder denitrifying conditions Oxindole was also detectedas a key intermediate of indole degradation by bacteriaconsortia under sulfate-reducing conditions methanogenicconditions [65 70] and denitrifying conditions [68]

To date only one pure culture of bacteria capable ofutilizing indole as its sole source of carbon and energythat is the sulfate reducer Desulfobacterium indolicum hasbeen isolated and characterized This bacterium was initiallyisolated from enriched marine sediments by Bak andWiddel[64] Several studies investigated indole degradation inDesul-fobacterium indolicum which degrades indole via oxindole[39 73] including Johansen et al [39] who proposed thebiodegradation pathway of indole for D indolicum Initiallyindole was hydroxylated at the C-2 position to form oxin-dole that was further hydroxylated at C-3 to form isatinIsatin underwent ring cleavage between the C-2 and C-3atoms on the pyrrole ring of indole to produce isatoic acidwhich was decarboxylated to anthranilic acid (Figure 5) Thefurther degradation of anthranilic acid achieved complete


NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid

23-Dihydroxybenzoic acid

Catechol

(a) (b)

NH2

NH2

Figure 4 Fungal degradation pathways of indole in (a) Aspergillus niger [12] and (b) Phomopsis liquidambari [38]

NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O

Isatin Isatoic acid Anthranilic acid

NH2

Figure 5 Anaerobic degradation pathway of indole in Desulfobacterium indolicum [39]


mineralization Similar results were reported for indoledegradation by a denitrifying microbial community [68]

Hong et al [74] studied two anaerobic indole-decom-posing microbial communities under both denitrifying andsulfate-reducing conditions In the denitrifying bioreactormost of the dominant bacteria were 120573-proteobacteria pre-dominantlyAlicycliphilusAlcaligenes andThauera genera Inthe sulfate-reducing bioreactor Clostridia andActinobacteriawere the dominating indole-degrading species [74]

3 Bacterial Degradation ofIndole-3-Acetic Acid

Several reports documented the bacterial transformationof indole-3-acetic acid [75ndash80] The decarboxylation ofindole-3-acetic acid to indole-3-methyl has been reportedin many rumen microorganisms including Lactobacillus sp[75] Clostridium scatologenes and Clostridium drakei [76]Jensen et al [77] reported the conversion of indole-3-aceticacid to 3-methylindole by a mixed population of pig fecalbacteria Attwood et al [78] reported production of 3-methylindole in the presence of indole-3-acetic acid by sixrumenmicroorganisms (similar to Prevotella spClostridiumsp Actinomyces sp and Megasphaera sp) isolated fromgrazing ruminants Ernstsen et al [79] showed the trans-formation of indole into indole-3-methanol in Rhizobiumphaseoli Tsubokura et al [80] reported the conversion ofindole-3-acetic acid to 2-formaminobenzoylacetic acid by abacterium isolated from air

The complete mineralization of indole-3-acetic acid hasalso been studied [40] four metabolic pathways for aero-bic degradation of indole-3-acetic acid were proposed andthese pathways involve two catechol pathways a gentisatepathway and an anthranilate pathway The catechol pathwayof indole-3-acetic acid degradation was initially studied ina Pseudomonas sp that degraded indole-3-acetic acid via3-methylindole 3-indoxyl salicylic acid and catechol [40]In this pathway indole-3-acetic acid was initially decar-boxylated to 3-methylindole which was converted to 3-hydroxyindole via hydroxylation and removal of methylgroup (Figure 6(a)) Subsequent hydroxylation and reductiongave 23-dihydroxy-dihydroindole which underwent ringcleavage and hydrolysis to produce salicylic acid whichwas then metabolized via catechol [40] Catechol is alsodetected as a metabolite of indole-3-acetic acid degradationby Pseudomonas putida 1290 [81] Pseudomonas sp LD2[82] and Arthrobacter sp [83] Another catechol pathway ofindole-3-acetic acid degradationwas studied in Pseudomonasputida 1290 which utilized indole-3-acetic acid as its solesource of carbon and energy and degraded indole-3-aceticacid with 2-hydroxy-indoleacetic acid dioxindole-3-aceticacid and catechol as intermediates (Figure 6(b)) [41 8485] The genes and enzymes involved in this pathway werecharacterized an 8994-bp DNA fragment containing ten iacgenes (iacABCDEFG iacHI and iacR) was responsible forindole-3-acetic acid degradation in Pseudomonas putida 1290[84 85] Scott et al [41] confirmed the role of iacA iacE andiacC in the degradation of indole-3-acetic acid the iacA geneproduct was involved in the first step of indole-3-acetic acid

degradation and catalyzed hydroxylation of the indole ringof indole-3-acetic acid the iacE gene product catalyzed thehydroxylation of 2-hydroxy-indole-3-acetic acid at position 3of the indole ring to produce dioxindole-3-acetic acid whichis the substrate of the iacC gene product [41] the iacR geneproduct is a transcriptional regulator controlling repressionor induction of the iac operons [41] the roles of the other iacgenes (iacB iacD iacE iacF iacG iacH and iacI) in thesesteps remain unknown

The gentisate pathway of indole-3-acetic acid degradationwas studied in Alcaligenes sp In 3 which degraded indole-3-acetic acid via isatin anthranilic acid and gentisic acid(Figure 6(c)) Similar metabolites were detected during thedegradation of indole by the same bacterium These datasuggest that Alcaligenes sp In 3 degraded both indole andindole-3-acetic acid via the gentisate pathway Jensen et al[42] reported the anthranilate pathway of indole-3-acetic aciddegradation in Bradyrhizobium japonicum which degradedindole-3-acetic acid via dioxindole-3-acetic acid dioxindoleisatin 2-aminophenyl glyoxylic acid (isatinic acid) andanthranilic acid (Figure 6(d))

The anaerobic degradation pathway of indole-3-aceticacid was studied in the denitrifying betaproteobacteriumAzoarcus evansii [43] The first step of this pathway is pro-duction of the enol and keto forms of 2-oxo-indole-3-aceticacid Initially a molybdenum cofactor-containing dehydro-genase catalyzed the hydroxylation of the N-heterocyclicpyrrole ring to produce the enol form of 2-oxo-indole-3-acetic acid [43] In the next step a hydantoinase-likeenzyme catalyzed the hydrolytic ring opening of the ketoform to form 2(21015840-aminophenyl)succinate (Figure 6(e)) Thenext step involves formation of 2(21015840-aminophenyl)succinyl-CoA catalyzed by the CoA ligase or the CoA trans-ferase The 2(21015840-aminophenyl)succinyl-CoA was rearrangedto produce 2-aminobenzylmalonyl-CoA catalyzed by acoenzyme B

12-dependent mutase Further degradation of

2-aminobenzylmalonyl-CoA leads to the formation of 2-aminobenzoyl-CoA or benzoyl-CoA [43] The 14 genesencoding proteins similar to indole-3-acetic acid-inducedproteins in Azoarcus evansii were identified in the genome ofAromatoleum aromaticum strain EbN1 [43]

Some bacteria promote plant growth by degrading exoge-nous indole-3-acetic acid in plant roots [86] for exam-ple Zuniga et al [86] reported that bacterial degradationof indole-3-acetic acid plays a key role in plant growth-promoting traits and is necessary for efficient rhizospherecolonization They reported that wild-type Burkholderiaphytofirmans promotes the growth of Arabidopsis plant rootsin the presence of exogenously added indole-3-acetic acidhowever a mutant strain with destructed iacC was unable topromote the growth of the plant root [86]

4 Bacterial Degradation of 4-Chloroindole

Only one bacterium is known for biodegradation of 4-chloroindole Arora and Bae [28] studied the degradationpathway of 4-chloroindole in Exiguobacterium sp PMAwhich utilized 4-chloroindole as its sole source of carbonand energy 4-Chloroindole was initially dehalogenated and


NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH

Indole-3-acetic acid 3-Methylindole 3-Hydroxyindole 23-Dihydroxy-dihydroindole Salicylic acid Catechol

CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH

Dioxindole-3-acetic acidIndole-3-acetic acid 2-Hydroxyindole-3-acetic acid Catechol

IacA IacE IacC

CH2COOH CH2COOH CH2COOH

(b)

NH N

H

O

OCOOH COOH

OH

HO

Indole-3-acetic acid Isatin Anthranilic acid Gentisic acid

CH2COOH

NH2

(c)

NH N

H

O

HO

Indole-3-acetic acid Dioxindole-3-acetic acid

NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH

Anthranilic acid2-Aminophenyl glyoxylic acid

CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA

Indole-3-acetic acid 2-Oxoindoleacetate enol form 2-Oxoindoleacetate keto form (2-Aminophenyl)succinate 2(2-Aminophenyl)succinyl-CoA

2-Aminobenzylmalonyl-CoA 2-Aminobenzoyl-CoA


NH2 NH2

NH2NH2NH2NH2NH2

(e)

Figure 6 Degradation pathways of indole-3-acetic acid in (a) a Pseudomonas sp [40] (b) Pseudomonas putida 1290 [41] (c) Alcaligenes spIn 3 [37] (d) Bradyrhizobium japonicum [42] (e) Azoarcus evansii [43]

further degradation of indole proceeded via isatin anthran-ilic acid and salicylic acid (Figure 7(a))The enzyme activitiesfor 4-chloroindole dehalogenase and anthranilic acid deam-inase were detected in the crude extract of the 4-chloroin-doles-induced cells of Exiguobacterium sp PMA confirm-ing indole and salicylic acid formation in the degradationpathway of 4-chloroindole Exiguobacterium sp PMA alsodegraded 4-chloroindole in sterile and nonsterile soil [28]The degradation rate was faster in sterile soil than in nonster-ile soil [28]

5 Bacterial Degradation of Methylindole

The degradation of 3-methylindole which is commonlyknown as skatole was studied in several bacteria [13] Kohdaet al [13] isolated three species of skatole-degrading Clostrid-ium (C aminovalericum C carnis and C malenominatum)from pig and chicken manure composting processes whichdegraded skatole from 300 to 800mgL Yin et al [87]reported biodegradation of 1-methylindole and 3-methy-lindole using enrichment cultures derived from mangrove


NH

Cl

NH N

H

O

O

COOHCOOH

OH

4-Chloroindole Indole Isatin

Anthranilic acidSalicylic acid

NH2

(a)

NH N

H

COOH

NH

OH

3-Methylindole Indoline-3-carboxylic acid Indoline-3-ol

CH3

(b)

NH N

H

O COOH

3-Methylindole 3-Methyloxindole

NH2

CH3 CH3 CH3

120572-Methyl-2-aminobenzeneacetic acid

(c)

Figure 7 Degradation pathway of (a) 4-chloroindole in Exiguobacterium sp PMA [28] (b) 3-methylindole in Pseudomonas sp GS [44] and(c) 3-methylindole by a sulfate reducing consortium [45]

sediment obtained from the Mai Po Nature Reserve ofHong Kong a pure culture of Pseudomonas aeruginosa Gsisolated from this enrichment utilized 1-methylindole and 3-methylindole as its sole source of carbon and energy and com-pletely degraded 1-methylindole and 3-methylindole aftermore than 40 days and 24 days respectively when the con-centration of 3-methylindole or 1-methylindole was 20mMin the culture [87] Indoline-3-carboxylic acid and indoline-3-ol were identified as metabolites of 3-methylindole in PaeruginosaGs (Figure 7(b)) [44] Gu and Berry [32] reportedthe degradation of 3-methylindole via 3-methyloxindoleusing a methanogenic consortium derived from enrichmentof wetland soil The removal of 3-methylindole was moni-tored by the four strains of lactic acid bacteria (Lactobacillusbrevis 112 (L brevis 112) L plantarum 102 L casei 6103 andL plantarumATCC8014) L brevis 112 was the best at remov-ing 3-methylindole [88] Gu et al [45] reported that a meth-anogenic bacterial consortia derived from marine sediment

from Victoria Harbour transformed 3-methylindole to 3-methyloxindole whereas a sulfate-reducing consortiummin-eralized 3-methylindole completely via 3-methyloxindole and120572ndashmethyl-2-aminobenzeneacetic acid (Figure 7(c))

Sharma et al [89] isolated a new 3-methylindole-degrad-ing purple nonsulfur bacteriumRhodopseudomonas palustrisWKU-KDNS3 from a swine waste lagoon using an enrich-ment technique This bacterium could remove gt93 of thetotal 3-methylindole in the medium by 21 days

6 Conclusions and Future Perspectives

(i) Microbes degrade indole either by mineralizationor cometabolism (biotransformation) In mineraliza-tion microbes utilized indole as the sole source ofcarbon and energy and degraded it completely via aseries of chemical reactions however in the process ofbiotransformation indole was transformed to other


compounds in the presence of an additional carbonsource These biotransformed products may be moreor less toxic than indole and sometimes used asuseful products for example several bacteria convertindole to indigo a compound of industrial value Sim-ilarly Arthrobacter sp SPG biotransformed indoleto indole-3-acetic acid (a plant growth-promotinghormone) indole-3-glyoxylic acid and indole-3-aldehyde A fewmicrobes adopt detoxification mech-anisms via biotransformation and convert indole toless toxic or nontoxic compounds for exampleCupri-avidus sp strain KK10 transformed indole to less toxicor nontoxic products via N-heterocyclic ring cleavageor carbocyclic aromatic ring cleavage

(ii) Three major pathways for aerobic bacterial mineral-ization of indole have been proposed However thegenes and the enzymes involved in these pathwayscould not yet be characterized

(iii) Anaerobic degradation of indole has been studiedunder methanogenic sulfate-reducing and denitrify-ing conditions However a few indole-mineralizingbacteria are known for anaerobic degradation ofindole More indole degrading anaerobic bacteriashould be isolated to understand the mechanism ofanaerobic degradation of indole

(iv) More biochemical studies should be carried out toelucidate the metabolic pathways of degradation of 4-chloroindole and methylindole

(v) Four major pathways of aerobic bacterial degradationof indole-3-acetic acid have been elucidated How-ever the genetics of bacterial degradation pathwayof indole-3-acetic acid was studied in Pseudomonasputida 1290 that contains iac gene cluster for indole-3-acetic acid degradation Furthermore completecharacterization of iac genes would be very helpfulto understand the mechanism of biodegradation ofindole-3-acetic acid

Conflict of Interests

The authors declare that they have no conflict of interests

Authorsrsquo Contribution

Pankaj Kumar Arora collected all the relevant publicationsarranged the general structure of the review drafted thepaper and produced figures Hanhong Bae and AshutoshShrama revised the paper

Acknowledgment

This work was carried out with the support of the Next-Generation Biogreen 21 Program (PJ011113) Rural Develop-ment Administration Republic of Korea

References

[1] W C Sumpter and F M Miller Heterocyclic Compounds withIndole and Carbazole Systems Wiley-Interscience AmsterdamThe Netherlands 1954

[2] S Budarari M J OrsquoNeil A Smith and P E HeckelmanThe Merck Index An Encyclopedia of Chemicals Drugs andBiologicalsMerckampCo NewYorkNYUSA 11th edition 1989

[3] G Collin and H Hoke ldquoIndolerdquo in Ullmanns Encyclopediaof Industrial Chemistry B Elvers S Hawkins M Ravenscroftand G Schulz Eds vol A14 pp 167ndash170 VCH WeinheimGermany 5th edition 1989

[4] L-J Yuan J-B Liu and X-G Xiao ldquoBiooxidation of indole andcharacteristics of the responsible enzymesrdquo African Journal ofBiotechnology vol 10 no 86 pp 19855ndash19863 2011

[5] N S Dailey ldquoProcess effluents quantities and control tech-nologiesrdquo in Environmental Health and Control Aspects of CoalConversionmdashAn Information Overview H M Braunstein E DCopenhaver and A Pfuderer Eds vol 1 pp 4100ndash4157 AnnArbor Science Publishers Ann Arbor Mish USA 1981

[6] K Winters R OrsquoDonnell J C Batterton and C Van BaalenldquoWater soluble components of four fuel oils chemical charac-terization and effects on growth of microalgaerdquoMarine Biologyvol 36 no 3 pp 269ndash276 1976

[7] K Grob and J A Voellmin ldquoGC-MS analysis of the lsquosemi-volatilesrsquo of cigarette smokerdquo Journal of Chromatographic Sci-ence vol 8 no 4 pp 218ndash220 1970

[8] I Florin L Rutberg M Curvall and C R Enzell ldquoScreening oftabacco smoke constituents for mutagenicity using the Amesrsquotestrdquo Toxicology vol 15 no 3 pp 219ndash232 1980

[9] M T Yokoyama and J R Carlson ldquoDissimilation of tryptophanand related indolic compounds by ruminal microorganisms invitrordquo Journal of Applied Microbiology vol 27 no 3 pp 540ndash548 1974

[10] N Mohammed R Onodera and M M Or-Rashid ldquoDegrada-tion of tryptophan and related indolic compounds by ruminalbacteria protozoa and their mixture in vitrordquo Amino Acids vol24 no 1-2 pp 73ndash80 2003

[11] J-H Lee ldquoIndole as an intercellular signal inmicrobial commu-nitiesrdquo FEMSMicrobiology Reviews vol 34 no 4 pp 426ndash4442010

[12] A J Kamath and C S Vaidyanathan ldquoNew pathway for thebiodegradation of indole in Aspergillus nigerrdquo Applied andEnvironmental Microbiology vol 56 no 1 pp 275ndash280 1990

[13] C Kohda T Ando and Y Nakai ldquoIsolation and characteriza-tion of anaerobic indole- and skatole-degrading bacteria fromcomposting animal wastesrdquoThe Journal of General and AppliedMicrobiology vol 43 no 5 pp 249ndash255 1997

[14] Y Nakai T Niino T Ando and C Kohda ldquoMicroorganismsaerobically degrading skatole or indole in composting pro-cessesrdquo Animal Science Journal vol 70 pp 32ndash37 1999

[15] S Fetzner ldquoBacterial degradation of pyridine indole quinolineand their derivatives under different redox conditionsrdquo AppliedMicrobiology and Biotechnology vol 49 no 3 pp 237ndash250 1998

[16] M Zhang J H Tay Y Qian and X S Gu ldquoCoke plant waste-water treatment by fixed biofilm system for COD and NH

3-N

removalrdquoWater Research vol 32 no 2 pp 519ndash527 1998[17] MOchiai KWakabayashi T Sugimura andMNagao ldquoMuta-

genicities of indole and 30 derivatives after nitrite treatmentrdquoMutation Research vol 172 no 3 pp 189ndash197 1986


[18] Y Sun and Y Li ldquoIndole and cholic acid effects on somebiochemical changes during dimethylhydrazine carcinogenesisin mice large intestinerdquo Chinese Medical Journal vol 100 no 8pp 636ndash638 1987

[19] T Niwa M Ise and T Miyazaki ldquoProgression of glomerularsclerosis in experimental uremic rats by administration ofindole a precursor of indoxyl sulfaterdquo American Journal ofNephrology vol 14 no 3 pp 207ndash212 1994

[20] M R Paradis R G Breeze W W Laegreid W M Bayly andD F Counts ldquoAcute hemolytic anemia induced by oral admin-istration of indole in poniesrdquo American Journal of VeterinaryResearch vol 52 no 5 pp 748ndash753 1991

[21] A CHammond J R Carlson andRG Breeze ldquoIndole toxicityin cattlerdquo Veterinary Record vol 107 no 15 pp 344ndash346 1980

[22] K S Rogers ldquoRabbit erythrocyte hemolysis by lipophilic arylmoleculesrdquo Proceedings of the Society for Experimental Biologyand Medicine vol 130 no 4 pp 1140ndash1142 1969

[23] K Riveles R Roza and P Talbot ldquoPhenols quinolines indolesbenzene and 2-cyclopenten-1-ones are oviductal toxicants incigarette smokerdquo Toxicological Sciences vol 86 no 1 pp 141ndash151 2005

[24] J C Forbes andRCNeale ldquoTheproduction of chronic arthritisby indole and other products of tryptophane putrefactionrdquoTheJournal of Laboratory and Clinical Medicine vol 22 no 9 pp921ndash924 1937

[25] I Nakoneczna J C Forbes andK S Rogers ldquoThe arthritogeniceffect of indole skatole and other tryptophan metabolites inrabbitsrdquo The American Journal of Pathology vol 57 no 3 pp523ndash538 1969

[26] H El-Shagi U Schulte and M H Zenk ldquoSpecific inhibition ofanthraquinone formation by amino compounds inMorinda cellculturesrdquo Naturwissenschaften vol 71 no 5 p 267 1984

[27] S Furukawa K Usuda M Abe and I Ogawa ldquoEffect of indole-3-acetic acid derivatives on neuroepithelium in rat embryosrdquoThe Journal of Toxicological Sciences vol 30 no 3 pp 165ndash1742005

[28] P K Arora and H Bae ldquoBiodegradation of 4-chloroindole byExiguobacterium sp PMArdquo Journal of HazardousMaterials vol284 pp 261ndash268 2015

[29] M Martın-Vivaldi A Pena J M Peralta-Sanchez et alldquoAntimicrobial chemicals in hoopoe preen secretions are pro-duced by symbiotic bacteriardquo Proceedings of the Royal Society BBiological Sciences vol 277 no 1678 pp 123ndash130 2010

[30] H G M Tiedink L H J De Haan W M F Jongen and JH Koeman ldquoIn-vitro testing and the carcinogenic potentialof several nitrosated indole compoundsrdquo Cell Biology andToxicology vol 7 no 4 pp 371ndash386 1991

[31] D L J Opdyke Ed Monographs on Fragrance Raw MaterialsPergamon Press New York NY USA 1979

[32] J-D Gu and D F Berry ldquoMetabolism of 3-methylindoleby a methanogenic consortiumrdquo Applied and EnvironmentalMicrobiology vol 58 no 8 pp 2667ndash2669 1992

[33] P K Arora and H Bae ldquoIdentification of new metabolites ofbacterial transformation of indole by gas chromatography-massspectrometry and high performance liquid chromatographyrdquoInternational Journal of Analytical Chemistry vol 2014 ArticleID 239641 5 pages 2014

[34] K Fukuoka K Tanaka Y Ozeki and R A Kanaly ldquoBiotrans-formation of indole by Cupriavidus sp strain KK10 proceedsthrough N-heterocyclic- and carbocyclic-aromatic ring cleav-age and production of indigoidsrdquo International Biodeteriorationand Biodegradation vol 97 pp 13ndash24 2015

[35] Y SakamotoMUchida andK Ichihara ldquoThe bacterial decom-position of indole (I) studies on its metabolic pathway bysuccessive adaptationrdquoMedical Journal of Osaka University vol3 pp 477ndash486 1953

[36] M Fujioka and H Wada ldquoThe bacterial oxidation of indolerdquoBiochimica et Biophysica ActamdashGeneral Subjects vol 158 no 1pp 70ndash78 1968

[37] G Claus and H J Kutzner ldquoDegradation of indole by Alcali-genes specrdquo Systematic and Applied Microbiology vol 4 no 2pp 169ndash180 1983

[38] Y Chen X-G Xie C-G Ren and C-C Dai ldquoDegradation ofN-heterocyclic indole by a novel endophytic fungus Phomopsisliquidambarirdquo Bioresource Technology vol 129 pp 568ndash5742013

[39] S S Johansen D Licht E ArvinHMosbaeligk andA BHansenldquoMetabolic pathways of quinoline indole and their methylatedanalogs by Desulfobacterium indolicum (DSM 3383)rdquo AppliedMicrobiology and Biotechnology vol 47 no 3 pp 292ndash300 1997

[40] M H Proctor ldquoBacterial dissimilation of indoleacetic acid anew route of breakdown of the indole nucleusrdquoNature vol 181no 4619 article 1345 1958

[41] J C Scott I V Greenhut and J H J Leveau ldquoFunctional char-acterization of the bacterial iac genes for degradation of theplant hormone indole-3-acetic acidrdquo Journal of Chemical Ecol-ogy vol 39 no 7 pp 942ndash951 2013

[42] J B Jensen H Egsgaard H vanOnckelen and B U JochimsenldquoCatabolism of indole-3-acetic acid and 4- and 5-chloroindole-3-acetic acid in Bradyrhizobium japonicumrdquo Journal of Bacteri-ology vol 177 no 20 pp 5762ndash5766 1995

[43] C Ebenau-Jehle MThomas G Scharf et al ldquoAnaerobic meta-bolism of indoleacetaterdquo Journal of Bacteriology vol 194 no 11pp 2894ndash2903 2012

[44] B Yin and J-D Gu ldquoAerobic degradation of 3-methylindole byPseudomonas aeruginosaGs isolated frommangrove sedimentrdquoHuman and Ecological Risk Assessment vol 12 no 2 pp 248ndash258 2006

[45] J-D Gu Y Fan andH Shi ldquoRelationship between structures ofsubstituted indolic compounds and their degradation bymarineanaerobic microorganismsrdquo Marine Pollution Bulletin vol 45no 1ndash12 pp 379ndash384 2002

[46] N Doukyu and R Aono ldquoBiodegradation of indole at highconcentration by persolvent fermentation with Pseudomonassp ST-200rdquo Extremophiles vol 1 no 2 pp 100ndash105 1997

[47] B Yin J-D Gu and N Wan ldquoDegradation of indole byenrichment culture and Pseudomonas aeruginosa Gs isolatedfrom mangrove sedimentrdquo International Biodeterioration andBiodegradation vol 56 no 4 pp 243ndash248 2005

[48] D Kim A Rahman I R Sitepu andYHashidoko ldquoAccelerateddegradation of exogenous indole byBurkholderia unamae strainCK43B exposed to pyrogallol-type polyphenolsrdquo BioscienceBiotechnology and Biochemistry vol 77 no 8 pp 1722ndash17272013

[49] C C R Allen D R Boyd M J Larkin K A Reid N DSharma and K Wilson ldquoMetabolism of naphthalene 1-naph-thol indene and indole by Rhodococcus sp strain NCIMB12038rdquo Applied and Environmental Microbiology vol 63 no 1pp 151ndash155 1997

[50] X Han W Wang and X Xiao ldquoMicrobial biosynthesis andbiotransformation of indigo and indigo-like pigmentsrdquo ChineseJournal of Biotechnology vol 24 no 6 pp 921ndash926 2008


[51] B D Ensley B J Ratzkin T D Osslund M J Simon LP Wackett and D T Gibson ldquoExpression of naphthaleneoxidation genes in Escherichia coli results in the biosynthesis ofindigordquo Science vol 222 no 4620 pp 167ndash169 1983

[52] RW Eaton andP J Chapman ldquoFormation of indigo and relatedcompounds from indolecarboxylic acids by aromatic acid-degrading bacteria chromogenic reactions for cloning genesencoding dioxygenases that act on aromatic acidsrdquo Journal ofBacteriology vol 177 no 23 pp 6983ndash6988 1995

[53] K-M Yen M R Karl L M Blatt et al ldquoCloning andcharacterization of a Pseudomonas mendocina KR1 gene clusterencoding toluene-4-monooxygenaserdquo Journal of Bacteriologyvol 173 no 17 pp 5315ndash5332 1991

[54] K E OrsquoConnor A DWDobson and S Hartmans ldquoIndigo for-mation by microorganisms expressing styrene monooxygenaseactivityrdquo Applied and Environmental Microbiology vol 63 no11 pp 4287ndash4291 1997

[55] E Moreno-Ruiz M J Hernaez O Martınez-Perez and ESantero ldquoIdentification and functional characterization of Sph-ingomonas macrogolitabida strain TFA genes involved in thefirst two steps of the tetralin catabolic pathwayrdquo Journal ofBacteriology vol 185 no 6 pp 2026ndash2030 2003

[56] H Pathak and D Madamwar ldquoBiosynthesis of indigo dye bynewly isolated naphthalene-degrading strain Pseudomonas spHOB1 and its application in dyeing cotton fabricrdquo AppliedBiochemistry and Biotechnology vol 160 no 6 pp 1616ndash16262010

[57] J P R Mercadal P Isaac F Sineriz and M A Ferrero ldquoIndigoproduction by Pseudomonas sp j26 a marine naphthalene-degrading strainrdquo Journal of Basic Microbiology vol 50 no 3pp 290ndash293 2010

[58] Y Wu S Q Zhang G H Ma D L Song and J Y Zhao ldquoStudyon biosynthesis of indigo involving transferring naphthaleneplasmid DNA from Pseudomonas to E colirdquo Acta GeneticaSinica vol 16 no 4 pp 318ndash324 1989

[59] Y Qu B Xu X Zhang et al ldquoBiotransformation of indole bywhole cells of recombinant biphenyl dioxygenase and biphenyl-23-dihydrodiol-23-dehydrogenaserdquo Biochemical EngineeringJournal vol 72 pp 54ndash60 2013

[60] L U Yan and M E I Lehe ldquoProduction of indigo by immo-bilization of E coli BL21 (DE3) cells in calcium-alginate gelcapsulesrdquo Chinese Journal of Chemical Engineering vol 15 no3 pp 387ndash390 2007

[61] H Keil C M Saint and P A Williams ldquoGene organization ofthe first catabolic operon of TOL plasmid pWW53 productionof indigo by the xylA gene productrdquo Journal of Bacteriology vol169 no 2 pp 764ndash770 1987

[62] H Nagayama T Sugawara R Endo et al ldquoIsolation of oxy-genase genes for indigo-forming activity from an artificiallypolluted soil metagenome by functional screening using Pseu-domonas putida strains as hostsrdquo Applied Microbiology andBiotechnology 2015

[63] P Katapodis M Moukouli and P Christakopoulos ldquoBiodegra-dation of indole at high concentration by persolvent fermenta-tion with the thermophilic fungus Sporotrichum thermophilerdquoInternational Biodeterioration and Biodegradation vol 60 no4 pp 267ndash272 2007

[64] F Bak and F Widdel ldquoAnaerobic degradation of indolic com-pounds by sulfate-reducing enrichment cultures and descrip-tion ofDesulfobacterium indolicum gen nov sp novrdquo Archivesof Microbiology vol 146 no 2 pp 170ndash176 1986

[65] J-D Gu Y Fan andH Shi ldquoRelationship between structures ofsubstituted indolic compounds and their degradation bymarineanaerobic microorganismsrdquo Marine Pollution Bulletin vol 45pp 379ndash384 2002

[66] E L Madsen A J Francis and J M Bollag ldquoEnvironmentalfactors affecting indole metabolism under anaerobic condi-tionsrdquo Applied and Environmental Microbiology vol 54 no 1pp 74ndash78 1988

[67] S M Liu W J Jones and J E Rogers ldquoInfluence of redoxpotential on the anaerobic biotransformation of nitrogen-heterocyclic compounds in anoxic freshwater sedimentsrdquoApplied Microbiology and Biotechnology vol 41 no 6 pp 717ndash724 1994

[68] E L Madsen and J-M Bollag ldquoPathway of indole metabolismby a denitrifying microbial communityrdquo Archives of Microbiol-ogy vol 151 no 1 pp 71ndash76 1988

[69] R Shanker and J-M Bollag ldquoTransformation of indole bymethanogenic and sulfate-reducing microorganisms isolatedfrom digested sludgerdquoMicrobial Ecology vol 20 no 2 pp 171ndash183 1990

[70] J-D Gu and D F Berry ldquoDegradation of substituted indoles byan indole-degrading methanogenic consortiumrdquo Applied andEnvironmental Microbiology vol 57 no 9 pp 2622ndash2627 1991

[71] Y-TWang M T Suidan and J T Pfeffer ldquoAnaerobic biodegra-dation of indole to methanerdquo Applied and EnvironmentalMicrobiology vol 48 no 5 pp 1058ndash1060 1984

[72] D F Berry E L Madsen and J-M Bollag ldquoConversion ofindole to oxindole under methanogenic conditionsrdquo Appliedand EnvironmentalMicrobiology vol 53 no 1 pp 180ndash182 1987

[73] D Licht S S Johansen E Arvin and B K Ahring ldquoTransfor-mation of indole and quinoline by Desulfobacterium indolicum(DSM 3383)rdquo Applied Microbiology and Biotechnology vol 47no 2 pp 167ndash172 1997

[74] X Hong X Zhang B Liu Y Mao Y Liu and L ZhaoldquoStructural differentiation of bacterial communities in indole-degrading bioreactors under denitrifying and sulfate-reducingconditionsrdquo Research in Microbiology vol 161 no 8 pp 687ndash693 2010

[75] M T Yokoyama and J R Carlson ldquoProduction of skatoleand para-cresol by a rumen Lactobacillus sprdquo Applied andEnvironmental Microbiology vol 41 no 1 pp 71ndash76 1981

[76] T R Whitehead N P Price H L Drake and M ACotta ldquoCatabolic pathway for the production of skatole andindoleacetic acid by the acetogen Clostridium drakei Clostrid-ium scatologenes and swine manurerdquo Applied and Environmen-tal Microbiology vol 74 no 6 pp 1950ndash1953 2008

[77] M T Jensen R P Cox and B B Jensen ldquo3-Methylindole(skatole) and indole production by mixed populations of pigfecal bacteriardquoApplied and Environmental Microbiology vol 61no 8 pp 3180ndash3184 1995

[78] G Attwood D Li D Pacheco and M Tavendale ldquoProductionof indolic compounds by rumen bacteria isolated from grazingruminantsrdquo Journal of Applied Microbiology vol 100 no 6 pp1261ndash1271 2006

[79] A Ernstsen G Sandberg A Crozier and C T WheelerldquoEndogenous indoles and the biosynthesis and metabolism ofindole-3-acetic acid in cultures of Rhizobium phaseolirdquo Plantavol 171 no 3 pp 422ndash428 1987

[80] S Tsubokura Y Sakamoto and K Ichihara ldquoThe bacterialdecomposition of indoleacetic acidrdquo The Journal of Biochem-istry vol 49 no 1 pp 38ndash42 1961


[81] J H J Leveau and S E Lindow ldquoUtilization of the plant hor-mone indole-3-acetic acid for growth by Pseudomonas putidastrain 1290rdquo Applied and Environmental Microbiology vol 71no 5 pp 2365ndash2371 2005

[82] LM Gieg A Otter and PM Fedorak ldquoCarbazole degradationby Pseudomonas sp LD2 metabolic characteristics and theidentification of some metabolitesrdquo Environmental Science andTechnology vol 30 no 2 pp 575ndash585 1996

[83] Y Mino ldquoStudies on destruction of indole-3-acetic acid by aspecies ofArthrobacter IV Decomposition productsrdquo Plant andCell Physiology vol 11 no 1 pp 129ndash138 1970

[84] J H J Leveau and S Gerards ldquoDiscovery of a bacterial genecluster for catabolism of the plant hormone indole 3-aceticacidrdquo FEMS Microbiology Ecology vol 65 no 2 pp 238ndash2502008

[85] G-H Lin H-P Chen J-H Huang et al ldquoIdentification andcharacterization of an indigo-producing oxygenase involved inindole 3-acetic acid utilization by Acinetobacter baumanniirdquoAntonie van Leeuwenhoek vol 101 no 4 pp 881ndash890 2012

[86] A ZunigaM J Poupin R Donoso et al ldquoQuorum sensing andindole-3-acetic acid degradation play a role in colonization andplant growth promotion of arabidopsis thaliana byBurkholderiaphytofirmans PsJNrdquo Molecular Plant-Microbe Interactions vol26 no 5 pp 546ndash553 2013

[87] B Yin L Huang and J D Gu ldquoBiodegradation of 1-methy-lindole and 3-methylindole by mangrove sediment enrichmentcultures and a pure culture of an isolated Pseudomonas aerugi-nosaGsrdquoWater Air and Soil Pollution vol 176 no ndash4 pp 185ndash199 2006

[88] X Meng Z-F He H-J Li and X Zhao ldquoRemoval of 3-methylindole by lactic acid bacteria in vitrordquo Experimental andTherapeutic Medicine vol 6 no 4 pp 983ndash988 2013

[89] N Sharma K Doerner P Alok and M Choudhary ldquoSkatoleremediation potential of Rhodopseudomonas palustris WKU-KDNS3 isolated from an animal waste lagoonrdquo Letters inApplied Microbiology vol 60 no 3 pp 298ndash306 2015

Submit your manuscripts athttpwwwhindawicom

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a metabolite of 3-methylindole generated in the humanintestine has possible psychotropic effects [31]

Indole and its derivatives are considered environmentalpollutants due to their toxicity and worldwide occurrencein soils coastal areas groundwater surface waters and evenindoor environments [15 32] Several reviews are availablefor applications andmicrobial production of indole howeverthere are very few reviews onmicrobial degradation of indole[4 11] Recently rapid progress was made in the study ofmicrobial degradation of indole and its derivatives and a fewnew pathways were proposed for microbial degradation ofindole and its derivatives [28 33 34] The aim of this reviewis to summarize the microbial degradation of indole indole-3-acetate 4-chloroindole and methylindole and highlightrecent developments in the field

2 Microbial Degradation of Indole

Microbial degradation of indole was investigated underaerobic and anaerobic conditions [12 13 15 33 34] Severalmechanisms were proposed for indole biodegradation bymicroorganisms including bacteria and fungi under aerobicconditions [12 35ndash37 46] microorganisms either mineral-ized indole completely [36 37 46] or transformed it intoother compounds in the presence of an additional carbonsource (cometabolism) [33 34] Under aerobic conditionsindole metabolism was generally initiated by oxidation ofindole followed by heterocyclic ring cleavage

21 Bacterial Mineralization of Indole A few indole-mineralizing bacteria have been isolated and characterizedfor aerobic biodegradation of indole [35ndash37 46]Threemajorpathways for indole mineralization have been proposed andthese pathways are the catechol pathway the gentisatepathway and the anthranilate pathwayThe catechol pathwaywas studied in an indole-mineralizing Gram-negativebacterium isolated from tap water [35] The first step of thecatechol pathway was hydroxylation of indole to indoxylwhich was further hydroxylated to 23-dihydroxyindole(Figure 1(a)) Further degradation proceeded via isatinN-formylanthranilic acid anthranilic acid salicylic acid andcatechol [35]The anthranilate pathway of indole degradationwas studied in a Gram-positive coccus that utilized indoleas its sole source of carbon and energy and degraded itvia 23-dihydroxyindole N-carboxyanthranilic acid andanthranilic acid (Figure 1(b)) [36] Claus and Kutzner [37]reported the gentisate pathway of indole degradation in anindole-mineralizing bacterium Alcaligenes sp In 3 isolatesfrom activated sludge In this pathway indole degradationoccurred via indoxyl isatin anthranilic acid and gentisicacid (Figure 1(c)) the formation of gentisic acid was a keyfeature of this pathway formed due to hydroxylation ofanthranilic acid The possibility of new indole degradationpathways aside from these 3 isolates has been suggestedDoukyu and Aono [46] reported the mineralization ofindole via isatin and isatic acid in Pseudomonas sp strainST-200 Yin et al [47] studied indole degradation in anindole-mineralizing bacterium Pseudomonas aeruginosaGs isolated from mangrove sediments and detected two

major metabolites however they could not identify eithermetabolite

22 Bacterial Cometabolism of Indole Cometabolism ofindole involves bacterial transformation of indole into othercompounds in the presence of additional carbon sourceThese biotransformed products may belong to one or moredegradation pathways of indole Fukuoka et al [34] studiedthe biotransformation of indole in Cupriavidus sp strainKK10 isolated from a soil bacterium consortium andproposed multiple pathways for indole biotransformationbased on the identified metabolites These pathways involveoxidation of indole followed by either N-heterocyclic ringcleavage or carbocyclic aromatic ring cleavage (Figure 2)In the carbocyclic aromatic ring cleavage pathway indolewas oxidized at the 4th and 5th positions to form 45-dihydroxyindole via cis-45-indole-dihydrodiol [34]The 45-dihydroxyindole underwent ortho- and meta-ring cleavageThe meta-ring cleavage product was identified as 4-(3-hydroxy-1H-pyrrol-2-yl)-2-oxo-but-3-enoic acid whereas 3-(2)-formyl-1H-pyrrole-2-(3)-carboxylic acid was identifiedas the ortho-ring cleavage product which was furthercarboxylated to pyrrole-23-dicarboxylic acid [34] The N-heterocyclic aromatic ring cleavage pathway followed oneof the following two mechanisms (i) monooxygenation ofindole at the 2 or 3 positions to form a corresponding indoxylthat further converted to a corresponding oxindole whichwas further transformed to isatin or (ii) dioxygenation ofindole at the 2 and 3 positions to form 23-dihydroxyindolevia indole-23-dihydrodiol [34] In the next step the isatinor 23-dihydroxyindole underwent N-heterocyclic ortho-ringcleavage to produce N-formylanthranilic acid which wasconverted to anthranilic acid Anthranilic acid was deami-nated to produce salicylic acid which was transformed togentisic acid via monohydroxylation The gentisic acid wasconverted to 124-trihydroxybenzene which could furtherproduce TCA cycle intermediates [34] The novel feature ofthis pathway is the previously unreported formation of 124-trihydroxybenzene Indigoids such as indigo indirubinisoindigo and 22-bis(31015840-indolyl) indoxyl were also biotrans-formation products of indole in Cupriavidus sp KK10 [34]

Another biotransformation pathway of indole was inves-tigated in Arthrobacter sp SPG Initially indole was bio-transformed into indole-3-acetic acid via a tryptophan-independent pathway [33] Indole-3-acetic acid was con-verted to indole-3-glyoxylic acid which was converted toindole-3-aldehyde (Figure 3(a)) Kim et al [48] reported thata plant polyphenol stimulated indole biotransformation inBurkholderia unamae CK43B isolated from the polyphenol-rich Shorea rhizosphere Polyphenol-exposed cells of strainCK43B utilized indole as a nitrogen source and degraded itvia anthranilic acid and catechol [48]

Indole can be biologically oxidized to indoxyl and thenindoxyl is spontaneously transformed to a dimer indigo(Figure 3(b)) a blue pigment [49 50]Manymicroorganismsinvolved in the transformation of indole into indigo havebeen isolated and characterized [49 50] including naph-thalene-degrading Pseudomonas putida PgG7 [51] m- andp-toluate-degrading P putida mt-2 [52] toluene-degrading


NH

NH

OH

NH

OH

OH

NH

O

O

COOH

NHCHO

COOH

COOH

OH

OH

OH

NH

OH

OH

COOH

NHCOOH

NH

OH

NH

O

O

COOH

COOH

OH

OH

COOH


23-Dihydroxyindole

Isatin


Anthranilic acid

Salicylic acid

Catechol

23-Dihydroxyindole


Anthranilic acid

Anthranilic acid

Isatin

Gentisic acid

(a)

(b)

(c)

NH2

NH2

NH2



NHN

H

OH

HOH

H

NH

OH

HO

HOOC

NHHOOC OHC

HOOC

NH

HOOC

HOOC

NH

HOOC

NH

HOOC

O

NH

OH

OH

H

H

NH

OH

OHCOOH

NH

OH

NH

OH

NH

O

NH

O

NH

O

O

OH

COOH

OH

COOH

HO

OH

OH

HO

TCA



Indole

3-Indoxyl 2-Indoxyl


Isatin





m-Ring cleavage

O-Ring cleavage


NH2






NH

NH

NH

COCOOH

NH

CHO


CH2COOH

(a)

NH

NH

OH

NH

ONH


(b)









NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid


Catechol

(a) (b)

NH2

NH2


NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O


NH2

















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

NH

OH

NH

OH

OH

NH

O

O

COOH

NHCHO

COOH

COOH

OH

OH

OH

NH

OH

OH

COOH

NHCOOH

NH

OH

NH

O

O

COOH

COOH

OH

OH

COOH


23-Dihydroxyindole

Isatin


Anthranilic acid

Salicylic acid

Catechol

23-Dihydroxyindole


Anthranilic acid

Anthranilic acid

Isatin

Gentisic acid

(a)

(b)

(c)

NH2

NH2

NH2



NHN

H

OH

HOH

H

NH

OH

HO

HOOC

NHHOOC OHC

HOOC

NH

HOOC

HOOC

NH

HOOC

NH

HOOC

O

NH

OH

OH

H

H

NH

OH

OHCOOH

NH

OH

NH

OH

NH

O

NH

O

NH

O

O

OH

COOH

OH

COOH

HO

OH

OH

HO

TCA



Indole

3-Indoxyl 2-Indoxyl


Isatin





m-Ring cleavage

O-Ring cleavage


NH2






NH

NH

NH

COCOOH

NH

CHO


CH2COOH

(a)

NH

NH

OH

NH

ONH


(b)









NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid


Catechol

(a) (b)

NH2

NH2


NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O


NH2

















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NHN

H

OH

HOH

H

NH

OH

HO

HOOC

NHHOOC OHC

HOOC

NH

HOOC

HOOC

NH

HOOC

NH

HOOC

O

NH

OH

OH

H

H

NH

OH

OHCOOH

NH

OH

NH

OH

NH

O

NH

O

NH

O

O

OH

COOH

OH

COOH

HO

OH

OH

HO

TCA



Indole

3-Indoxyl 2-Indoxyl


Isatin





m-Ring cleavage

O-Ring cleavage


NH2






NH

NH

NH

COCOOH

NH

CHO


CH2COOH

(a)

NH

NH

OH

NH

ONH


(b)









NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid


Catechol

(a) (b)

NH2

NH2


NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O


NH2

















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

NH

NH

COCOOH

NH

CHO


CH2COOH

(a)

NH

NH

OH

NH

ONH


(b)









NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid


Catechol

(a) (b)

NH2

NH2


NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O


NH2

















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

NH

O

NH

O

O

NH

O

OHH

COOH

NH

OH

NHCHO

COOH

COOH

OH

COOH

OH

OH

OH

Indole

Oxindole

Isatin

Dioxindole

Anthranilic acid

3-Indoxyl


Anthranilic acid


Catechol

(a) (b)

NH2

NH2


NH

NH

O

NH

COOH

COOH

COOH

Indole Oxindole

NH

O

O


NH2

















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of
















NH

NH N

H

OH

NH

OH

OH

H

H OH

COOH

OH

OH


CH2COOH CH3

(a)

NH N

H

OH

NH

O

HO

OH

OH


IacA IacE IacC


(b)

NH N

H

O

OCOOH COOH

OH

HO


CH2COOH

NH2

(c)

NH N

H

O

HO


NH

H

O

HO

Dioxindole

NH

O

O

Isatin

COCOOH COOH


CH2COOH CH2COOH

NH2 NH2

(d)

NH

NH

OHNH

O COOH

COOH

COSCoA

COOH

COOHCOSCoA

COSCoACOSCoA

OH

COSCoA

OCOSCoA




NH2 NH2

NH2NH2NH2NH2NH2

(e)






NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH

Cl

NH N

H

O

O

COOHCOOH

OH



NH2

(a)

NH N

H

COOH

NH

OH


CH3

(b)

NH N

H

O COOH


NH2

CH3 CH3 CH3


(c)

















Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of











Acknowledgment


References

















3-N























































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





















































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

review article microbial degradation of indole and...

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