3-Ketosteroid 9α-hydroxylase enzymes: Rieske non-heme monooxygenases essential for bacterial steroid degradation
详细信息 查看全文
- 作者：Mirjan Petrusma (1)
Robert van der Geize (1)
Lubbert Dijkhuizen (1) - 关键词：3 ; Ketosteroid 9α ; hydroxylase ; Rieske mono ; oxygenase ; 9α ; Hydroxylation ; Rhodococcus ; Mycobacterium ; Steroid biotransformation
- 刊名：Antonie van Leeuwenhoek
- 出版年：2014
- 出版时间：July 2014
- 年：2014
- 卷：106
- 期：1
- 页码：157-172
- 全文大小：
- 参考文献：1. Andor A, Jekkel A, Hopwood DA, Jeanplong F, Ilkoy E, K?nya A, Kurucz I, Ambrus G (2006) Generation of useful insertionally blocked sterol degradation pathway mutants of fast-growing mycobacteria and cloning, characterization, and expression of the terminal oxygenase of the 3-ketosteroid 9alpha-hydroxylase in / Mycobacterium smegmatis mc2155. Appl Environ Microbiol 72:6554-559 CrossRef
2. Arima K, Nagasawa M, Bae M, Tamura M (1969) Microbial transformation of sterols. Part I. Decomposition of cholesterol by microorganisms. Agric Biol Chem 33:1636-643 CrossRef
3. Arnell R, Johannisson R, Lindholm J, Fornstedt T, Ersson B, Ballagi A, Caldwell K (2007) Biotechnological approach to the synthesis of 9alpha-hydroxylated steroids. Prep Biochem Biotechnol 37:309-21 CrossRef
4. Barry SM, Challis GL (2013) Mechanism and catalytic diversity of rieske non-heme iron-dependent oxygenases. ACS Catal 3(10) (Review). doi:non-url-ref">10.1021/cs400087p
5. Batie CJ, Ballou DP, Correll CJ (1991) Phthalate dioxygenase reductase and related flavin-iron-sulfur containing electron transferases. In: Müller F (ed) Chemistry and biochemistry of flavoenzymes. CRC Press, Boca Raton, pp 543-56
6. Beharry ZM, Eby DM, Coulter ED, Viswanathan R, Neidle EL, Phillips RS, Kurtz DM Jr (2003) Histidine ligand protonation and redox potential in the Rieske dioxygenases: role of a conserved aspartate in anthranilate 1,2-dioxygenase. Biochemistry 42:13625-3636 CrossRef
7. Boyd DR, Sharma ND, Byrne BE, Haughey SA, Kennedy MA, Allen CC (2004) Dioxygenase-catalysed oxidation of alkylaryl sulfides: sulfoxidation versus cis-dihydrodiol formation. Org Biomol Chem 2:2530-537 CrossRef
8. Bragin EY, Shtratnikova VY, Dovbnya DV, Schelkunov MI, Pekov YA, Malakho SG, Egorova OV, Ivashina TV, Sokolov SL, Ashapkin VV, Donova MV (2013) Comparative analysis of genes encoding key steroid core oxidation enzymes in fast-growing / Mycobacterium spp. strains. J Steroid Biochem Mol Biol 138:41-3 CrossRef
9. Breskvar K, Cresnar B, Plaper A, Hudnik-Plevnik T (1991) Localization of the gene encoding steroid hydroxylase cytochrome P-450 from / Rhizopus nigricans inside a / HindIII fragment of genomic DNA. Biochem Biophys Res Commun 178:1078-083 CrossRef
10. Bruijnincx PC, van Koten G, Klein Gebbink RJ (2008) Mononuclear non-heme iron enzymes with the 2-His-1-carboxylate facial triad: recent developments in enzymology and modeling studies. Chem Soc Rev 37:2716-744 (Review) CrossRef
11. Capyk JK, Eltis LD (2012) Phylogenetic analysis reveals the surprising diversity of an oxygenase class. J Biol Inorg Chem 17:425-36 CrossRef
12. Capyk JK, D’Angelo I, Strynadka NC, Eltis LD (2009) Characterization of 3 ketosteroid 9α-hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of / Mycobacterium tuberculosis. J Biol Chem 284:9937-946 CrossRef
13. Capyk JK, Casabon I, Gruninger R, Strynadka NC, Eltis LD (2011) Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in / Mycobacterium tuberculosis. J Biol Chem 286:40717-0724 CrossRef
14. Chakraborty J, Ghosal D, Dutta A, Dutta TK (2012) An insight into the origin and functional evolution of bacterial aromatic ring-hydroxylating oxygenases. J Biomol Struct Dyn 30:419-36 CrossRef
15. Correll CC, Batie CJ, Ballou DP, Ludwig ML (1992) Phthalate dioxygenase reductase: a modular structure for electron transfer from pyridine nucleotides to [2Fe-S]. Science 258:1604-610 CrossRef
16. Costa S, Giovannini PP, Fantin G, Medici A, Pedrini P (2013a) New 9,10-secosteroids from biotransformations of hyodeoxycholic acid with / Rhodococcus spp. Helv Chim Acta 96:1062 CrossRef
17. Costa S, Giovannini PP, Fantin G, Medici A, Pedrini P (2013b) New 9,10-Secosteroids from biotransformations of bile acids with / Rhodococcus ruber. Helv Chim Acta 96:2124 CrossRef
18. Donova MV (2007) Transformation of steroids by actinobacteria: a review. Appl Biochem Microbiol 43:1-4 (Review) CrossRef
19. Donova MV, Egorova OV (2012) Microbial steroid transformations: current state and prospects. Appl Microbiol Biotechnol 94:1423-447 (Review) CrossRef
20. Dresen C, Lin LY, D’Angelo I, Tocheva EI, Strynadka N, Eltis LD (2010) A flavin-dependent monooxygenase from / Mycobacterium tuberculosis involved in cholesterol catabolism. J Biol Chem 285:22264-2270 CrossRef
21. Driscoll MD, McLean KJ, Levy C, Mast N, Pikuleva IA, Lafite P, Rigby SE, Leys D, Munro AW (2010) Structural and biochemical characterization of / Mycobacterium tuberculosis CYP142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen. J Biol Chem 285:38270-8282 CrossRef
22. Fernandes P, Cruz A, Angelova B, Pinheiro HM, Cabral JMS (2003) Microbial conversion of steroid compounds: recent developments. Enzyme Microb Technol 32:688-05 (Review) CrossRef
23. Ferraro DJ, Gakhar L, Ramaswamy S (2005) Rieske business: structure-function of Rieske non-heme oxygenases. Biochem Biophys Res Commun 338:175-90 (Review) CrossRef
24. Ferraro DJ, Okerlund AL, Mowers JC, Ramaswamy S (2006) Structural basis for regioselectivity and stereoselectivity of product formation by naphthalene 1,2-dioxygenase. J Bacteriol 188:6986-994 CrossRef
25. Friemann R, Ivkovic-Jensen MM, Lessner DJ, Yu CL, Gibson DT, Parales RE, Eklund H, Ramaswamy S (2005) Structural insight into the dioxygenation of nitroarene compounds: the crystal structure of nitrobenzene dioxygenase. J Mol Biol 348:1139-151 CrossRef
26. Furukawa K, Suenaga H, Goto M (2004) Biphenyl dioxygenases: functional versatilities and directed evolution. J Bacteriol 186:5189-196 (Review) CrossRef
27. Gibson DT, Wang KC, Sih CJ, Whitlock H Jr (1966) Mechanisms of steroid oxidation by microorganisms. IX. On the mechanism of ring A cleavage in the degradation of 9,10-seco steroids by microorganisms. J Biol Chem 241:551-59
28. Harayama S, Kok M, Neidle EL (1992) Functional and evolutionary relationships among diverse oxygenases. Annu Rev Microbiol 46:565-01 (Review) CrossRef
29. Hegg EL, Que L Jr (1997) The 2-His-1-carboxylate facial triad–an emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur J Biochem 250:625-29 (Review) CrossRef
30. Holland HL (1999) Recent advances in applied and mechanistic aspects of the enzymatic hydroxylation of steroids by whole-cell biocatalysts. Steroids 64:178-86 (Review) CrossRef
31. Horinouchi M, Hayashi T, Kudo T (2012) Steroid degradation in / Comamonas testosteroni. J Steroid Biochem Mol Biol 129:4-4 CrossRef
32. Hu Y, van der Geize R, Besra GS, Gurcha SS, Liu A, Rohde M, Singh M, Coates A (2010) 3-Ketosteroid 9alpha-hydroxylase is an essential factor in the pathogenesis of / Mycobacterium tuberculosis. Mol Microbiol 75:107-21 CrossRef
33. Itagaki E, Hatta T, Wakabayashi T, Suzuki K (1990) Spectral properties of 3-ketosteroid-delta 1-dehydrogenase from / Nocardia corallina. Biochim Biophys Acta 1040:281-86 CrossRef
34. Iyer LM, Koonin EV, Aravind L (2001) Adaptations of the helix-grip fold for ligand binding and catalysis in the START domain superfamily. Proteins 43:134-44 CrossRef
35. Jiang H, Parales RE, Gibson DT (1999) The alpha subunit of toluene dioxygenase from / Pseudomonas putida F1 can accept electrons from reduced FerredoxinTOL but is catalytically inactive in the absence of the beta subunit. Appl Environ Microbiol 65:315-18
36. Kano S, Tanaka K, Hibino S, Shibuya S (1979) New synthesis of cortico steroids from 17-ketosteroids: application and stereochemical study of the unsaturated sulfoxide-sulfenate rearrangement. J Org Chem 44:1582-584
37. Karlsson A, Parales JV, Parales RE, Gibson DT, Eklund H, Ramaswamy S (2003) Crystal structure of naphthalene dioxygenase: side-on binding of dioxygen to iron. Science 299:1039-042 CrossRef
38. Klink M, Brzezinska M, Szulc I, Brzostek A, Kielbik M, Sulowska Z, Dziadek J (2013) Cholesterol oxidase is indispensable in the pathogenesis of / Mycobacterium tuberculosis. PLoS One 8:e73333. doi:non-url-ref">10.1371/journal.pone.0073333 CrossRef
39. Knol J, Bodewits K, Hessels GI, Dijkhuizen L, van der Geize R (2008) 3-Keto-5alpha-steroid delta(1)-dehydrogenase from / Rhodococcus erythropolis SQ1 and its orthologue in / Mycobacterium tuberculosis H37Rv are highly specific enzymes that function in cholesterol catabolism. Biochem J 410:339-46 CrossRef
40. Kumamaru T, Suenaga H, Mitsuoka M, Watanabe T, Furukawa K (1998) Enhanced degradation of polychlorinated biphenyls by directed evolution of biphenyl dioxygenase. Nat Biotechnol 16:663-66 CrossRef
41. Kweon O, Kim SJ, Baek S, Chae JC, Adjei MD, Baek DH, KimY C, Cerniglia CE (2008) A new classification system for bacterial Rieske non-heme iron aromatic ring-hydroxylating oxygenases. BMC Biochem 9:11 CrossRef
42. Lack NA, Yam KC, Lowe ED, Horsman GP, Owen RL, Sim E, Eltis LD (2010) Characterization of a carbon–carbon hydrolase from / Mycobacterium tuberculosis involved in cholesterol metabolism. J Biol Chem 285:434-43 CrossRef
43. Lee K, Brand JM, Gibson DT (1995) Stereospecific sulfoxidation by toluene and naphthalene dioxygenases. Biochem Biophys Res Commun 212:9-5 CrossRef
44. Locher HH, Leisinger T, Cook AM (1991) 4-Sulphobenzoate 3,4-dioxygenase. Purification and properties of a desulphonative two-component enzyme system from / Comamonas testosteroni T-2. Biochem J 274:833-42
45. Madyastha KM, Joseph T (1993) Studies on the 14 alpha-hydroxylation of progesterone in / Mucor piriformis. J Steroid Biochem Mol Biol 45:563-69 CrossRef
46. Mahato SB, Garai S (1997) Advances in microbial steroid biotransformation. Steroids 62:332-45 (Review) CrossRef
47. Malaviya A, Gomes J (2008) Androstenedione production by biotransformation of phytosterols. Bioresour Technol 99:6725-737 (Review) CrossRef
48. Mason JR, Cammack R (1992) The electron transport proteins of hydroxylating bacterial dioxygenases. Ann Rev Microbiol 46:277-05 (Review) CrossRef
49. Mathieu JM, Mohn WW, Eltis LD, LeBlanc JC, Stewart GR, Dresen C, Okamoto K, Alvarez PJ (2010) 7-Ketocholesterol catabolism by / Rhodococcus jostii RHA1. Appl Environ Microbiol 76:352-55 CrossRef
50. McLeod MP, Warren RL, Hsiao WW, Araki N, Myhre M, Fernandes C, Miyazawa D, Wong W, Lillquist AL, Wang D, Dosanjh M, Hara H, Petrescu A, Morin RD, Yang G, Stott JM, Schein JE, Shin H, Smailus D, Siddiqui AS, Marra MA, Jones SJ, Holt R, Brinkman FS, Miyauchi K, Fukuda M, Davies JE, Mohn WW, Eltis LD (2006) The complete genome of / Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse. Proc Natl Acad Sci USA 103:15582-5587 CrossRef
51. Meena LS, Rajni (2010) Survival mechanisms of pathogenic / Mycobacterium tuberculosis H37Rv. FEBS J 277:2416-427 (Review) CrossRef
52. Megges R, Müller-Frohne M, Pfeil D, Ruckpaul K (1990) In: Ruckpaul K, Rein H (eds) Microbial steroid hydroxylation enzymes in glucocorticoid production. Akademie Verlag, Berlin (Review)
53. Mohn WW, Wilbrink MH, Casabon I, Stewart GR, Liu J, van der Geize R, Eltis LD (2012) Gene cluster encoding cholate catabolism in / Rhodococcus spp. J Bacteriol 194:6712-719 CrossRef
54. Nagasawa M, Bae M, Tamura G, Arima K (1969) Microbial transformation of sterols. II. Cleavage of sterol side chains by microorganisms. Agric Biol Chem 33:1644-650 CrossRef
55. Nakatsu CH, Straus NA, Wyndham RC (1995) The nucleotide sequence of the Tn5271 3-chlorobenzoate 3,4-dioxygenase genes (cbaAB) unites the class IA oxygenases in a single lineage. Microbiology (UK) 141:485-95 CrossRef
56. Nam JW, Nojiri H, Yoshida T, Habe H, Yamane H, Omori T (2001) New classification system for oxygenase components involved in ring-hydroxylating oxygenations. Biosci Biotechnol Biochem 65:254-63 CrossRef
57. Neidig ML, Solomon EI (2005) Structure-function correlations in oxygen activating non-heme iron enzymes. Chem Commun (Camb). 47:5843-863 (Review) CrossRef
58. Neidle EL, Hartnett C, Ornston LN, Bairoch A, Rekik M, Harayama S (1991) Nucleotide sequences of the / Acinetobacter calcoaceticus / benABC genes for benzoate 1,2-dioxygenase reveal evolutionary relationships among multicomponent oxygenases. J Bacteriol 173:5385-395
59. Nesbitt NM, Yang X, Fontán P, Kolesnikova I, Smith I, Sampson NS, Dubnau E (2010) A thiolase of / Mycobacterium tuberculosis is required for virulence and production of androstenedione and androstadienedione from cholesterol. Infect Immun 78:275-82 CrossRef
60. Nojiri H, Nam JW, Kosaka M, Morii KI, Takemura T, Furihata K, Yamane H, Omori T (1999) Diverse oxygenations catalyzed by carbazole 1,9a-dioxygenase from / Pseudomonas sp. Strain CA10. J Bacteriol 181:3105-113
61. Nojiri H, Ashikawa Y, Noguchi H, Nam JW, Urata M, Fujimoto Z, Uchimura H, Terada T, Nakamura S, Shimizu K, Yoshida T, Habe H, Omori T (2005) Structure of the terminal oxygenase component of angular dioxygenase, carbazole 1,9α-dioxygenase. J Mol Biol 351:355-70 CrossRef
62. Ouellet H, Guan S, Johnston JB, Chow ED, Kells PM, Burlingame AL, Cox JS, Podust LM, de Montellano PR (2010) / Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one. Mol Microbiol 77:730-42 CrossRef
63. Pandey AK, Sassetti CM (2008) Mycobacterial persistence requires the utilization of host cholesterol. Proc Natl Acad Sci USA 105:4376-380 CrossRef
64. Parales RE (2003) The role of active-site residues in naphthalene dioxygenase. J Ind Microbiol Biotechnol 30:271-78 (Review) CrossRef
65. Parales RE, Parales JV, Gibson DT (1999) Aspartate 205 in the catalytic domain of naphthalene dioxygenase is essential for activity. J Bacteriol 181:1831-837
66. Peterson DH, Murray HC (1952) Microbiological oxygenation of steroids at carbon-11. J Am Chem Soc 74:1871-872 CrossRef
67. Petrusma M (2011) Exploring 3-ketosteroid 9α-hydroxylases of Rhodococcus rhodochrous DSM43269: biochemical, physiological, molecular and structural characterization of a key enzyme in bacterial steroid degradation. Dissertation, University of Groningen
68. Petrusma M, Dijkhuizen L, van der Geize R (2009) / Rhodococcus rhodochrous DSM 43269 3-ketosteroid 9α-hydroxylase, a two-component iron-sulfur-containing monooxygenase with subtle steroid substrate specificity. Appl Environ Microbiol 75:5300-307 CrossRef
69. Petrusma M, Hessels GI, Dijkhuizen L, van der Geize R (2011) Multiplicity of 3-ketosteroid-9α-hydroxylase enzymes in / Rhodococcus rhodochrous DSM43269 for the specific degradation of different classes of steroids. J Bacteriol 193:3931-940 CrossRef
70. Petrusma M, Dijkhuizen L, van der Geize R (2012) Structural features in the KshA terminal oxygenase protein determining substrate preference of 3-ketosteroid 9α-hydroxylase enzymes. J Bacteriol 194:115-21 CrossRef
71. Pinto A, Tarasev M, Ballou DP (2006) Substitutions of the “bridging-aspartate 178 result in profound changes in the reactivity of the Rieske center of phthalate dioxygenase. Biochemistry 45:9032-041 CrossRef
72. Rengarajan J, Bloom BR, Rubin EJ (2005) Genome-wide requirements for / Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA 102:8327-332 CrossRef
73. Resnick SM, Gibson DT (1993) Biotransformation of anisole and phenetole by aerobic hydrocarbonoxidizing bacteria. Biodegradation 4:195-03 CrossRef
74. Ros?oniec KZ, Wilbrink MH, Capyk JK, Mohn WW, Ostendorf M, van der Geize R, Dijkhuizen L, Eltis LD (2009) Cytochrome P450 125 (CYP125) catalyses C26-hydroxylation to initiate sterol side-chain degradation in / Rhodococcus jostii RHA1. Mol Microbiol 74:1031-043 CrossRef
75. Sassetti CM, Rubin EJ (2003) Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci USA 100:12989-2994 CrossRef
76. Schnappinger D, Ehrt S, Voskuil MI, Liu Y, Mangan JA, Monahan IM, Dolganov G, Efron B, Butcher PD, Nathan C, Schoolnik GK (2003) Transcriptional adaptation of / Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J Exp Med 198:693-04 CrossRef
77. Sih CJ, Tai HH, Tsong YY, Lee SS, Coombe RG (1968) Mechanisms of steroid oxidation by microorganisms. XIV. Pathway of cholesterol side-chain degradation. Biochemistry 7:808-18 CrossRef
78. S?hngen NL (1913) Benzin, Petroleum, Paraffino1 and Paraffin als Kohlenstoff-und Energiequelle fur Mikroben. Zentbl Bakt Parasitenk (Abt. II) 37:595
79. Strijewski A (1982) The steroid-9 alpha-hydroxylation system from / Nocardia species. Eur J Biochem 128:125-35 CrossRef
80. Suzuki K, Sanga K, Chikaoka Y, Itagaki E (1993) Purification and properties of cytochrome P-450 (P-450lun) catalyzing steroid 11 beta-hydroxylation in / Curvularia lunata. Biochim Biophys Acta 1203:215-23 CrossRef
81. Sydor PK, Barry SM, Odulate OM, Barona-Gomez F, Haynes SW, Corre C, Song L, Challis GL (2011) Regio- and stereodivergent antibiotic oxidative carbocyclizations catalysed by Rieske oxygenase-like enzymes. Nat Chem 3:388-92 CrossRef
82. Tarasev M, Pinto A, Kim D, Elliott SJ, Ballou DP (2006) The “bridging-aspartate 178 in phthalate dioxygenase facilitates interactions between the Rieske center and the iron(II)-mononuclear center. Biochemistry 45:10208-0216 CrossRef
83. Tarasev M, Kaddis CS, Yin S, Loo JA, Burgner J, Ballou DP (2007) Similar enzymes, different structures: phthalate dioxygenase is an alpha3alpha3 stacked hexamer, not an alpha3beta3 trimer like “normal-Rieske oxygenases. Arch Biochem Biophys 466:31-9 CrossRef
84. Torok DS, Resnick SM, Brand JM, Cruden DL, Gibson DT (1995) Desaturation and oxygenation of 1,2-dihydronaphthalene by toluene and naphthalene dioxygenase. J Bacteriol 177:5799-805
85. Uchimura H, Horisaki T, Umeda T, Noguchi H, Usami Y, Li L, Terada T, Nakamura S, Shimizu K, Takemura T, Habe H, Furihata K, Omori T, Yamane H, Nojiri H (2008) Alteration of the substrate specificity of the angular dioxygenase carbazole 1,9α-dioxygenase. Biosci Biotechnol Biochem 72:3237-248 CrossRef
86. Van der Geize R, Dijkhuizen L (2004) Harnessing the catabolic diversity of rhodococci for environmental and biotechnological applications. Curr Opin Microbiol 7:255-61 (Review)
87. Van der Geize R, Hessels GI, van Gerwen R, Vrijbloed JW, van Der Meijden P, Dijkhuizen L (2000) Targeted disruption of the kstD gene encoding a 3-ketosteroid delta(1)-dehydrogenase isoenzyme of / Rhodococcus erythropolis strain SQ1. Appl Environ Microbiol 66:2029-036 CrossRef
88. Van der Geize R, Hessels GI, van Gerwen R, van der Meijden P, Dijkhuizen L (2001) Unmarked gene deletion mutagenesis of / kstD, encoding 3-ketosteroid Δ1-dehydrogenase, in / Rhodococcus erythropolis SQ1 using / sacB as counter-selectable marker. FEMS Microbiol Lett 205:197-02 CrossRef
89. Van der Geize R, Hessels GI, Van Gerwen R, Van der Meijden P, Dijkhuizen L (2002) Molecular and functional characterization of kshA and kshB, encoding two components of 3-ketosteroid 9α-hydroxylase, a class IA monooxygenase, in / Rhodococcus erythropolis strain SQ1. Mol Microbiol 45:1007-018 CrossRef
90. Van der Geize R, Yam K, Heuser T, Wilbrink MH, Hara H, Anderton MC, Sim E, Dijkhuizen L, Davies JE, Mohn WW, Eltis LD (2007) A gene cluster encoding cholesterol catabolism in a soil actinomycete provides insight into / Mycobacterium tuberculosis survival in macrophages. Proc Natl Acad Sci USA 104:1947-952 CrossRef
91. Van der Geize R, Hessels GI, Nienhuis-Kuiper M, Dijkhuizen L (2008) Characterization of a second / Rhodococcus erythropolis SQ1 3-ketosteroid 9alpha-hydroxylase activity comprising a terminal oxygenase homologue, KshA2, active with oxygenase-reductase component KshB. Appl Environ Microbiol 74:7197-203 CrossRef
92. Wang FQ, Yao K, Wei DZ (2011) From soybean phytosterols to steroid hormones. Soybean Health. InTech—Open Access Publisher, Rijeka, pp 232-52 (Review)
93. Wang PH, Lee TH, Ismail W, Tsai CY, Lin CW, Tsai YW, Chiang YR (2013) An oxygenase-independent cholesterol catabolic pathway operates under oxic conditions. PLoS One 8:e66675 CrossRef
94. Wilbrink MH, Petrusma M, Dijkhuizen L, van der Geize R (2011) FadD19 of / Rhodococcus rhodochrous DSM43269: a steroid-CoA ligase essential for degradation of C24-branched sterol side chains. Appl Environ Microbiol 77:4455-464 CrossRef
95. Yam KC, D’Angelo I, Kalscheuer R, Zhu H, Wang JX, Snieckus V, Ly LH, Converse PJ, Jacobs WR Jr, Strynadka N, Eltis LD (2009) Studies of a ring-cleaving dioxygenase illuminate the role of cholesterol metabolism in the pathogenesis of / Mycobacterium tuberculosis. PLoS Pathog 5(e1000344):5
96. Yam KC, Okamoto S, Roberts JN, Eltis LD (2011) Adventures in / Rhodococcus—from steroids to explosives. Can J Microbiol 57:155-68 (Review) CrossRef
97. Yang X, Gao J, Smith I, Dubnau E, Sampson NS (2011) Cholesterol is not an essential source of nutrition for / Mycobacterium tuberculosis during infection. J Bacteriol 193:1473-476 CrossRef - 作者单位：Mirjan Petrusma (1)
Robert van der Geize (1)
Lubbert Dijkhuizen (1)
1. Department of Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands - ISSN：1572-9699
文摘
Various micro-organisms are able to use sterols/steroids as carbon- and energy sources for growth. 3-Ketosteroid 9α-hydroxylase (KSH), a two component Rieske non-heme monooxygenase comprised of the oxygenase KshA and the reductase KshB, is a key-enzyme in bacterial steroid degradation. It initiates opening of the steroid polycyclic ring structure. The enzyme has industrial relevance in the synthesis of pharmaceutical steroids. Deletion of KSH activity in sterol degrading bacteria results in blockage of steroid ring opening and is used to produce valuable C19-steroids such as 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione. Interestingly, KSH activity is essential for the pathogenicity of Mycobacterium tuberculosis. Detailed information about KSH thus is of medical relevance, and KSH inhibitory compounds may find application in combatting tuberculosis. In recent years, the 3D structure of the KshA protein of M. tuberculosis H37Rv has been elucidated and various studies report biochemical characteristics and possible physiological roles of KSH. The current knowledge is reviewed here and forms a solid basis for further studies on this highly interesting enzyme. Future work may result in the construction of KSH mutants capable of production of specific bioactive steroids. Furthermore, KSH provides an promising target for drugs against the pathogenic agent M. tuberculosis.