Applied Microbiology and Biotechnology

, Volume 103, Issue 10, pp 3965–3978 | Cite as

Remarkable diversification of bacterial azoreductases: primary sequences, structures, substrates, physiological roles, and biotechnological applications

  • Hirokazu SuzukiEmail author


Azoreductases reductively cleave azo linkages by using NAD(P)H as an electron donor. The enzymes are widely found in bacteria and act on numerous azo dyes, which allow various unique applications. This review describes primary amino acid sequences, structures, substrates, physiological roles, and biotechnological applications of bacterial azoreductases to discuss their remarkable diversification. According to primary sequences, azoreductases were classified phylogenetically into four main clades. Most members of clades I–III are flavoproteins, whereas clade IV members include flavin-free azoreductases. Clades I and II prefer NADPH and NADH, respectively, as electron donors, whereas other members generally use both. Several enzymes formed no clades; moreover, some bacteria produce azoreductases with longer primary structures than those hitherto identified, which implies further diversification of bacterial azoreductases. The crystal structures commonly reveal the Rossmann folds; however, ternary structures are moderately varied with different quaternary conformation. Although physiological roles are obscure, several azoreductases have been shown to act on metabolites such as flavins, quinones, and metal ions more efficiently than on azo dyes. Considering that many homologs exclusively act on these metabolites, it is possible that azoreductases are actually side activities of versatile reductases that act on various substrates with different specificities. In parallel, this idea raises the possibility that homologous enzymes, even if these are already defined as other types of reductases, widely harbor azoreductase activities. Although azoreductases for which their genes have been identified are not abundant, it may be simple to identify azoreductases of biotechnological importance that have novel substrate specificities.


Azo dye Classification Flavoprotein Oxidoreductase Reductase Nicotinamide 


Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals conducted by the author.


  1. Bafana A, Chakrabarti T (2008) Lateral gene transfer in phylogeny of azoreductase enzyme. Comput Biol Chem 32:191–197. Google Scholar
  2. Bafana A, Chakrabarti T, Devi SS (2008) Azoreductase and dye detoxification activities of Bacillus velezensis strain AB. Appl Microbiol Biotechnol 77:1139–1144. Google Scholar
  3. Bin Y, Jiti Z, Jing W, Cuihong D, Hongman H, Zhiyong S, Yongming B (2004) Expression and characteristics of the gene encoding azoreductase from Rhodobacter sphaeroides AS1.1737. FEMS Microbiol Lett 236:129–136. Google Scholar
  4. Blümel S, Stolz A (2003) Cloning and characterization of the gene coding for the aerobic azoreductase from Pigmentiphaga kullae K24. Appl Microbiol Biotechnol 62:186–190. Google Scholar
  5. Blümel S, Busse H, Stolz A, Kämpfer P (2001a) Xenophilus azovorans gen. nov., sp. nov., a soil bacterium that is able to degrade azo dyes of the Orange II type. Int J Syst Evol Microbiol 51:1831–1837. Google Scholar
  6. Blümel S, Mark B, Busse H, Kämpfer P, Stolz A (2001b) Pigmentiphaga kullae gen. nov., sp. nov., a novel member of the family Alcaligenacea with the ability to decolorize azo dyes aerobically. Int J Syst Evol Microbiol 51:1867–1871. Google Scholar
  7. Blümel S, Knackmuss H, Stolz A (2002) Molecular cloning and characterization of the gene coding for the aerobic azoreductase from Xenophilus azovorans KF46F. Appl Environ Microbiol 68:3948–3955. Google Scholar
  8. Brown SD, Thompson MR, VerBerkmoes NC, Chourey K, Shah M, Zhou J, Hettich RL, Thompson DK (2006) Molecular dynamics of the Shewanella oneidensis response to chromate stress. Mol Cell Proteomics 5:1054–1071. Google Scholar
  9. Bürger S, Stolz A (2010) Characterisation of the flavin-free oxygen-tolerant azoreductase from Xenophilus azovorans KF46F in comparison to flavin-containing azoreductases. Appl Microbiol Biotechnol 87:2067–2076. Google Scholar
  10. Canevari M, Castagliuolo I, Brun P, Cardin M, Schiavon M, Pasut G, Veronese FM (2009) Poly(ethylene glycol)-mesalazine conjugate for colon specific delivery. Int J Pharm 368:171–177. Google Scholar
  11. Cao X, Di M, Wang J (2017) Expansion of the active site of the azoreductase from Shewanella oneidensis MR-1. J Mol Graph Model 78:213–220. Google Scholar
  12. Carceller E, Salas J, Merlos M, Giral M, Ferrando R, Escamilla I, Ramis J, García–Rafanell J, Forn J (2001) Novel azo derivatives as prodrugs of 5-aminosalicylic acid and amino derivatives with potent platelet activating factor antagonist activity. J Med Chem 44:3001–3013. Google Scholar
  13. Chalansonnet V, Mercier C, Orenga S, Gilbert C (2017) Identification of Enterococcus faecalis enzymes with azoreductases and/or nitroreductase activity. BMC Microbiol 17:126. Google Scholar
  14. Chen H (2006) Recent advances in azo dye degrading enzyme research. Curr Protein Pept Sci 7:101–111. Google Scholar
  15. Chen H, Wang R, Cerniglia CE (2004) Molecular cloning, overexpression, purification, and characterization of an aerobic FMN-dependent azoreductase from Enterococcus faecalis. Protein Expr Purif 34:302–310. Google Scholar
  16. Chen H, Hopper SL, Cerniglia CE (2005) Biochemical and molecular characterization of an azoreductase from Staphylococcus aureus, a tetrameric NADPH-dependent flavoprotein. Microbiology 151:1433–1441. Google Scholar
  17. Chen H, Xu H, Kweon O, Chen S, Cerniglia CE (2008) Functional role of Trp-105 of Enterococcus faecalis azoreductase (AzoA) as resolved by structural and mutational analysis. Microbiology 154:2659–2667. Google Scholar
  18. Chen H, Feng JH, Kweon O, Xu H, Cerniglia CE (2010) Identification and molecular characterization of a novel flavin-free NADPH preferred azoreductase encoded by azoB in Pigmentiphaga kullae K24. BMC Biochem 11:13. Google Scholar
  19. Chengalroyen MD, Dabbs ER (2013) The microbial degradation of azo dyes: minireview. World J Microbiol Biotechnol 29:389–399. Google Scholar
  20. Crescente V, Holland SM, Kashyap S, Polycarpou E, Sim E, Ryan A (2016) Identification of novel members of the bacterial azoreductase family in Pseudomonas aeruginosa. Biochem J 473:549–558. Google Scholar
  21. Deller S, Sollner S, Trenker-El-Toukhy R, Jelesarov I, Gübitz GM, Macheroux P (2006) Characterization of a thermostable NADPH:FMN oxidoreductase from the mesophilic bacterium Bacillus subtilis. Biochemistry 45:7083–7091. Google Scholar
  22. Eslami M, Amoozegar MA, Asad S (2016) Isolation, cloning and characterization of an azoreductase from the halophilic bacterium Halomonas elongata. Int J Biol Macromol 85:111–116. Google Scholar
  23. Feng J, Cerniglia CE, Chen H (2012a) Toxicological significance of azo dye metabolism by human intestinal microbiota. Front Biosci 1:568–586. Google Scholar
  24. Feng J, Kweon O, Xu H, Cerniglia CE, Chen H (2012b) Probing the NADH- and methyl red-binding site of a FMN-dependent azoreductase (AzoA) from Enterococcus faecalis. Arch Biochem Biophys 520:99–107. Google Scholar
  25. Ferri S, Kojima K, Sode K (2011) Review of glucose oxidases and glucose dehydrogenases: a bird’s eye view of glucose sensing enzymes. J Diabetes Sci Technol 5:1068–1076. Google Scholar
  26. Fouts JR, Kamm JJ, Brodie BB (1957) Enzymatic reduction of prontosil and other azo dyes. J Pharmacol Exp Ther 120:291–300. Google Scholar
  27. Gao F, Ding H, Shao L, Xu X, Zhao Y (2015) Molecular characterization of a novel thermal stable reductase capable of decoloration of both azo and triphenylmethane dyes. Appl Microbiol Biotechnol 99:255–267. Google Scholar
  28. Gonçalves AMD, Mendes S, de Sanctis D, Martins LO, Bento I (2013) The crystal structure of Pseudomonas putida azoreductase – the active site revisited. FEBS J 280:6643–6657.
  29. Green JRB, Lobo AJ, Holdsworth CD, Leicester RJ, Gibson JA, Kerr GD, Hodgson HJF, Parkins KJ, Taylor MD (1998) Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. Gastroenterology 114:15–22. Google Scholar
  30. Han L, Liang B (2018) New approaches to NAD(P)H regeneration in the biosynthesis systems. World J Microbiol Biotechnol 34:141. Google Scholar
  31. Hua J, Yu L (2019) Cloning and characterization of a flavin-free oxygen-insensitive azoreductase from Klebsiella oxytoca GS-4-08. Biotechnol 41:371–378.
  32. Ito K, Nakanishi M, Lee W, Sasaki H, Zenno S, Saigo K, Kitade Y, Tanokura M (2006) Three-dimensional structure of AzoR from Escherichia coli. J Biol Chem 281:20567–20576. Google Scholar
  33. Ito K, Nakanishi M, Lee W, Zhi Y, Sasaki H, Zenno S, Saigo K, Kitade Y, Tanokura M (2008) Expansion of substrate specificity and catalytic mechanism of azoreductase by X-ray crystallography and site-directed mutagenesis. J Biol Chem 283:13889–13896. Google Scholar
  34. Jang M, Lee Y, Kim C, Lee J, Kang D, Kim S, Lee Y (2005) Triphenylmethane reductase from Citrobacter sp. strain KCTC 18061P: purification, characterization, gene cloning, and overexpression of a functional protein in Escherichia coli. Appl Environ Microbiol 71:7955–7960. Google Scholar
  35. Jilani JA, Shomaf M, Alzoubi KH (2013) Synthesis and evaluation of mutual azo prodrug of 5-aminosalicylic acid linked to 2-phenylbenzoxazole-2-yl-5-acetic acid in ulcerative colitis. Drug Des Devel Ther 7:691–698. Google Scholar
  36. Johansson HE, Johansson MK, Wong AC, Armstrong ES, Peterson EJ, Grant RE, Roy MA, Reddington MV, Cook RM (2011) BTI1, an azoreductase with pH-dependent substrate specificity. Appl Environ Microbiol 77:4223–4225. Google Scholar
  37. Kelley KD, Olive LQ, Hadziselimovic A, Sanders CR (2010) Look and see if it is time to induce protein expression in Escherichia coli cultures. Biochemistry 49:5405–5407. Google Scholar
  38. Kim MH, Kim Y, Park H, Lee JS, Kwak S, Jung W, Lee S, Kim D, Lee Y, Oh T (2008) Structural insight into bioremediation of triphenylmethane dyes by Citrobacter sp. triphenylmethane reductase. J Biol Chem 283:31981–31990. Google Scholar
  39. Kobori T, Sasaki H, Lee WC, Zenno S, Saigo K, Murphy MEP, Tanokura M (2001) Structure and site-directed mutagenesis of a flavoprotein from Escherichia coli that reduces nitrocompounds. J Biol Chem 276:2816–2823. Google Scholar
  40. Kwak YH, Lee DS, Kim HB (2003) Vibrio harveyi nitroreductase is also a chromate reductase. Appl Environ Microbiol 69:4390–4395. Google Scholar
  41. Lang W, Sirisansaneeyakul S, Ngiwsara L, Mendes S, Martins LO, Okuyama M, Kimura A (2013) Characterization of a new oxygen-insensitive azoreductase from Brevibacillus laterosporus TISTR1911: toward dye decolorization using a packed-bed metal affinity reactor. Bioresour Technol 150:298–306. Google Scholar
  42. Liger D, Graille M, Zhou C, Leulliot N, Quevillon-Cheruel S, Blondeau K, Janin J, van Tilbeurgh H (2004) Crystal structure and functional characterization of yeast YLR011wp, an enzyme with NAD(P)H-FMN and ferric iron reductase activities. J Biol Chem 279:34890–34897. Google Scholar
  43. Liu G, Zhou J, Lv H, Xiang X, Wang J, Zhou M, Qv Y (2007a) Azoreductase from Rhodobacter sphaeroides AS1.1737 is a flavodoxin that also functions as nitroreductase and flavin mononucleotide reductase. Appl Microbiol Biotechnol 76:1271–1279. Google Scholar
  44. Liu Z, Chen H, Shaw N, Hopper SL, Chen L, Chen S, Cerniglia CE, Wang B (2007b) Crystal structure of an aerobic FMN-dependent azoreductase (AzoA) from Enterococcus faecalis. Arch Biochem Biophys 463:68–77. Google Scholar
  45. Liu G, Zhou J, Jin R, Zhou M, Wang J, Lu H, Qu Y (2008a) Enhancing survival of Escherichia coli by expression of azoreductase AZR possessing quinone reductase activity. Appl Microbiol Biotechnol 80:409–416. Google Scholar
  46. Liu G, Zhou J, Wang J, Yan B, Li J, Lu H, Qu Y, Jin R (2008b) Site-directed mutagenesis of substrate binding sites of azoreductase from Rhodobacter sphaeroides. Biotechnol Lett 30:869–875. Google Scholar
  47. Liu G, Zhou J, Fu QS, Wang J (2009) The Escherichia coli azoreductase AzoR is involved in resistance to thiol-specific stress caused by electrophilic quinones. J Bacteriol 191:6394–6400. Google Scholar
  48. Macwana SR, Punj S, Cooper J, Schwenk E, John GH (2010) Identification and isolation of an azoreductase from Enterococcus faecium. Curr Issues Mol Biol 12:43–48. Google Scholar
  49. Mahmood S, Khalid A, Arshad M, Mahmood T, Crowley DE (2016) Detoxification of azo dyes by bacterial oxidoreductase enzymes. Crit Rev Biotechnol 36:639–651. Google Scholar
  50. Maier J, Kandelbauer A, Erlacher A, Cavaco–Paulo A, Gübitz GM (2004) A new alkali-thermostable azoreductase from Bacillus sp. strain SF. Appl Environ Microbiol 70:837–844. Google Scholar
  51. Matsumoto K, Mukai Y, Ogata D, Shozui F, Nduko JM, Taguchi S, Ooi T (2010) Characterization of thermostable FMN-dependent NADH azoreductase from the moderate thermophile Geobacillus stearothermophilus. Appl Microbiol Biotechnol 86:1431–1438. Google Scholar
  52. Medina SH, Chevliakov MV, Tiruchinapally G, Durmaz YY, Kuruvilla SP, ElSayed MEH (2013) Enzyme-activated nanoconjugates for tunable release of doxorubicin in hepatic cancer cells. Biomaterials 34:4655–4666. Google Scholar
  53. Mendes S, Pereira L, Batista C, Martins LO (2011) Molecular determinants of azo reduction activity in the strain Pseudomonas putida MET94. Appl Microbiol Biotechnol 92:393–405. Google Scholar
  54. Mercier C, Chalansonnet V, Orenga S, Gilbert C (2013) Characteristics of major Escherichia coli reductases involved in aerobic nitro and azo reduction. J Appl Microbiol 115:1012–1022. Google Scholar
  55. Misal SA, Gawai KR (2018) Azoreductase: a key player of xenobiotic metabolism. Bioresour Bioprocess 5:17. Google Scholar
  56. Misal SA, Lingojwar DP, Gawai KR (2013) Properties of NAD(P)H azoreductase from alkaliphilic red bacteria Aquiflexum sp. DL6. Protein J 32:601–608. Google Scholar
  57. Misal SA, Lingojwar DP, Lokhande MN, Lokhande PD, Gawai KR (2014) Enzymatic transformation of nitro-aromatic compounds by a flavin-free NADH azoreductase from Lysinibacillus sphaericus. Biotechnol Lett 36:127–131. Google Scholar
  58. Morrison JM, John GH (2015) Non-classical azoreductase secretion in Clostridium perfringens in response to sulfonated azo dye exposure. Anaerobe 34:34–43. Google Scholar
  59. Morrison JM, Wright CM, John GH (2012) Identification, isolation and characterization of a novel azoreductase from Clostridium perfringens. Anaerobe 18:229–234. Google Scholar
  60. Mugerfeld I, Law BA, Wickham GS, Thompson DK (2009) A putative azoreductase gene is involved in the Shewanella oneidensis response to heavy metal stress. Appl Microbiol Biotechnol 82:1131–1141. Google Scholar
  61. Nakanishi M, Yatome C, Ishida N, Kitade Y (2001) Putative ACP phosphodiesterase gene (acpD) encodes an azoreductase. J Biol Chem 276:46394–46399. Google Scholar
  62. Nishiya Y, Yamamoto Y (2007) Characterization of a NADH:dichloroindophenol oxidoreductase from Bacillus subtilis. Biosci Biotechnol Biochem 71:611–614. Google Scholar
  63. Ooi T, Shibata T, Sato R, Ohno H, Kinoshita S, Thuoc TL, Taguchi S (2007) An azoreductase, aerobic NADH-dependent flavoprotein discovered from Bacillus sp.: functional expression and enzymatic characterization. Appl Microbiol Biotechnol 75:377–386. Google Scholar
  64. Ooi T, Shibata T, Matsumoto K, Kinoshita S, Taguchi S (2009) Comparative enzymatic analysis of azoreductases from Bacillus sp. B29. Biosci Biotechnol Biochem 73:1209–1211. Google Scholar
  65. Punj S, John GH (2009) Purification and identification of an FMN-dependent NAD(P)H azoreductase from Enterococcus faecalis. Curr Issues Mol Biol 11:59–65. Google Scholar
  66. Qi J, Schlömann M, Tischler D (2016) Biochemical characterization of an azoreductase from Rhodococcus opacus 1CP possessing methyl red degradation ability. J Mol Catal B Enzym 130:9–17. Google Scholar
  67. Qi J, Paul CE, Hollmann F, Tischler D (2017) Changing the electron donor improves azoreductase dye degrading activity at neutral pH. Enzyme Microb Technol 100:17–19. Google Scholar
  68. Qureshi AI, Cohen RD (2005) Mesalamine delivery systems: do they really make much difference? Adv Drug Deliv Rev 57:281–302. Google Scholar
  69. Rafii F, Cerniglia CE (1993) Comparison of the azoreductase and nitroreductase from Clostridium perfringens. Appl Environ Microbiol 59:1731–1734. Google Scholar
  70. Rafii F, Franklin W, Cerniglia CE (1990) Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora. Appl Environ Microbiol 56:2146–2151Google Scholar
  71. Rao J, Khan A (2013) Enzyme sensitive synthetic polymer micelles based on the azobenzene motif. J Am Chem Soc 135:14056–14059. Google Scholar
  72. Rao J, Hottinger C, Khan A (2014) Enzyme-triggered cascade reactions and assembly of abiotic block copolymers into micellar nanostructures. J Am Chem Soc 136:5872–5875. Google Scholar
  73. Roldán MD, Pérez–Reinado E, Castillo F, Moreno–Vivián C (2008) Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev 32:474–500. Google Scholar
  74. Ruiz JFM, Radics G, Windle H, Serra HO, Simplicío AL, Kedziora K, Fallon PG, Kelleher DP, Gilmer JF (2009) Design, synthesis, and pharmacological effects of a cyclization-activated steroid prodrug for colon targeting in inflammatory bowel disease. J Med Chem 52:3205–3211. Google Scholar
  75. Ruiz JFM, Kedziora K, Keogh B, Maguire J, Reilly M, Windle H, Kelleher DP, Gilmer JF (2011) A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors. Bioorg Med Chem Lett 21:6636–6640. Google Scholar
  76. Ruiz JFM, Kedziora K, O’Reilly M, Maguire J, Keogh B, Windle H, Kelleher DP, Gilmer JF (2012) Azo-reductase activated budesodine prodrugs for colon targeting. Bioorg Med Chem Lett 22:7573–7577. Google Scholar
  77. Ryan A (2017) Azoreductases in drug metabolism. Br J Pharmacol 174:2161–2173. Google Scholar
  78. Ryan A, Laurieri N, Westwood I, Wang C, Lowe E, Sim E (2010a) A novel mechanism for azoreduction. J Mol Biol 400:24–37. Google Scholar
  79. Ryan A, Wang C, Laurieri N, Westwood I, Sim E (2010b) Reaction mechanism of azoreductases suggests convergent evolution with quinone oxidoreductases. Protein Cell 1:780–790. Google Scholar
  80. Ryan A, Kaplan E, Laurieri N, Lowe E, Sim E (2011) Activation of nitrofurazone by azoreductases: multiple activities in one enzyme. Sci Rep 1(63).
  81. Ryan A, Kaplan E, Nebel J, Polycarpou E, Crescente V, Lowe E, Preston GM, Sim E (2014) Identification of NAD(P)H quinone oxidoreductase activity in azoreductases from P. aeruginosa: azoreductases and NAD(P)H quinone oxidoreductases belong to the same FMN-dependent superfamily of enzymes. PLoS One 9:e98551. Google Scholar
  82. Sakuma S, Lu Z, Kopečková P, Kopeček J (2001) Biorecognizable HPMA copolymer-drug conjugates for colon-specific delivery of 9-aminocamptothecin. J Control Release 75:365–379. Google Scholar
  83. Sandhya S, Sarayu K, Uma B, Swaminathan K (2008) Decolorizing kinetics of a recombinant Escherichia coli SS125 strain harboring azoreductase gene from Bacillus latrosporus RRK1. Bioresour Technol 99:2187–2191. Google Scholar
  84. Shin N, Hanaoka K, Piao W, Miyakawa T, Fujisawa T, Takeuchi S, Takahashi S, Komatsu T, Ueno T, Terai T, Tahara T, Tanokura M, Nagano T, Urao Y (2017) Development of an azoreductase-based reporter system with synthetic fluorogenic substrates. ACS Chem Biol 12:558–563. Google Scholar
  85. Shinagawa E (2011) Purification and characterization of Fe(III)-EDTA reductase from Bacillus sp. B-3. Biosci Biotechnol Biochem 75:2063–2065. Google Scholar
  86. Sugiura W, Yoda T, Matsuba T, Tanaka Y, Suzuki Y (2006) Expression and characterization of the genes encoding azoreductases from Bacillus subtilis and Geobacillus stearothermophilus. Biosci Biotechnol Biochem 70:1655–1665. Google Scholar
  87. Suzuki H (2018) Peculiarities and biotechnological potential of environmental adaptation by Geobacillus species. Appl Microbiol Biotechnol 102:10425–10437. Google Scholar
  88. Suzuki Y, Yoda T, Ruhul A, Sugiura W (2001) Molecular cloning and characterization of the gene coding for azoreductase from Bacillus sp. OY1-2 isolated from soil. J Biol Chem 276:9059–9065. Google Scholar
  89. Suzuki H, Abe T, Doi K, Ohshima T (2018) Azoreductase from alkaliphilic Bacillus sp. AO1 catalyzes indigo reduction. Appl Microbiol Biotechnol 102:9171–9181. Google Scholar
  90. Tang J, Huang C, Shu J, Zheng J, Ma D, Li J, Yang R (2018) Azoreductase and target simultaneously activated fluorescent monitoring for cytochrome c release under hypoxia. Anal Chem 90:5865–5872. Google Scholar
  91. Teruel AH, Pérez–Esteve É, González–Álvarez I, González–Álvarez M, Costero AM, Ferri D, Parra M, Gaviña P, Merino V, Martínez–Mañez R, Sancenón F (2018) Smart gated magnetic silica mesoporous particles for targeted colon drug delivery: new approaches for inflammatory bowel diseases treatment. J Control Release 281:58–69. Google Scholar
  92. Thompson MR, VerBerkmoes NC, Chourey K, Shah M, Thompson DK, Hettich RL (2007) Dosage-dependent proteome response of Shewanella oneidensis MR-1 to acute chromate challenge. J Proteome Res 6:1745–1757. Google Scholar
  93. Töwe S, Leelakriangsak M, Kobayashi K, Van Duy N, Hecker M, Zuber P, Antelmann H (2007) The MarR-type repressor MhqR (YkvE) regulates multiple dioxyaenases/glyoxalases and an azoreductase which confer resistance to 2-methylhydroquinone and catechol in Bacillus subtilis. Mol Microbiol 66:40–54. Google Scholar
  94. Van den Mooter G, Samyn C, Kinget R (1994) The relation between swelling properties and enzymatic degradation of azo polymers designed for colon-specific drug delivery. Pharm Res 11:1737–1741. Google Scholar
  95. Vorontsov II, Minasov G, Brunzelle JS, Shuvalova L, Kiryukhina O, Collart FR, Anderson WF (2007) Crystal structure of an apo form of Shigella flexneri ArsH protein with an NADPH-dependent FMN reductase activity. Protein Sci 16:2483–2490. Google Scholar
  96. Wang C, Hagemeier C, Rahman N, Lowe E, Noble M, Coughtrie M, Sim E, Westwood I (2007) Molecular cloning, characterisation and ligand-bound structure of an azoreductase from Pseudomonas aeruginosa. J Mol Biol 373:1213–1228. Google Scholar
  97. Wang C, Laurieri N, Abuhammad A, Lowe E, Westwood I, Ryan A, Sim E (2010) Role of tyrosine 131 in the active site of paAzoR1, an azoreductase with specificity for the inflammatory bowel disease prodrug balsalazide. Acta Crystallogr Sect F Struct Biol Cryst Commun 66:2–7. Google Scholar
  98. Whangsuk W, Toewiwat N, Dubbs J, Sallabhan R, Mongkolsuk S, Loprasert S (2018) Identification of a repressor and an activator of azoreductase gene expression in Pseudomonas putida and Xanthomonas oryzae. Biochem Biophys Res Commun 502:9–14. Google Scholar
  99. Yang Y, Lu L, Gao F, Zhao Y (2013a) Characterization of an efficient catalytic and organic solvent-tolerant azoreductase toward methyl red from Shewanella oneidensis MR-1. Environ Sci Pollut Res 20:3232–3239. Google Scholar
  100. Yang Y, Wei B, Zhao Y, Wang J (2013b) Construction of an integrated enzyme system consisting azoreductase and glucose 1-dehydrogenase for dye removal. Bioresour Technol 130:517–521. Google Scholar
  101. Ye J, Yang H, Rosen BP, Bhattacharjee H (2007) Crystal structure of the flavoprotein ArsH from Sinorhizobium meliloti. FEBS Lett 581:3996–4000. Google Scholar
  102. Yu J, Ogata D, Gai Z, Taguchi S, Tanaka I, Ooi T, Yao M (2014) Structures of AzrA and of AzrC complexed with substrate or inhibitor: insight into substrate specificity and catalytic mechanism. Acta Crystallogr D Struct Biol 70:553–564. Google Scholar
  103. Yu L, Zhang X, Xie T, Hu J, Wang S, Li W (2015) Intracellular azo decolorization is coupled with aerobic respiration by a Klebsiella oxytoca strain. Appl Microbiol Biotechnol 99:2431–2439. Google Scholar
  104. Zbaida S, Levine WG (1990) Characteristics of two classes of azo dye reductase activity associated with rat liver microsomal cytochrome P450. Biochem Pharmacol 40:2415–2423. Google Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Faculty of EngineeringTottori UniversityTottoriJapan
  2. 2.Center for Research on Green Sustainable ChemistryTottori UniversityTottoriJapan

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