Biosynthesis of a steroid metabolite by an engineered Rhodococcus erythropolis strain expressing a mutant cytochrome P450 BM3 enzyme

Applied Microbiology and Biotechnology

Volumn 99, Issue 11, 2015, Pages 4713-4721

  Venkataraman, Harini ^a   te Poele, Evelien M ^b   Rosłoniec, Kamila Z ^b   Vermeulen, Nico ^a   Commandeur, Jan N M ^a   van der Geize, Robert ^b   Dijkhuizen, Lubbert ^b  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

^b UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

Cytochrome P450 BM3 M02 enzyme; Norandrostenedione; Rhodococcus erythropolis; Steroids; Whole cell bioconversion

Indexed keywords

BIOCHEMISTRY; BIOCONVERSION; CELLS; CYTOLOGY; HYDROXYLATION; METABOLITES;

CYTOCHROME P450 BM3; NORANDROSTENEDIONE; RHODOCOCCUS ERYTHROPOLIS; STEROIDS; WHOLE CELL;

ENZYMES;

ANDROSTANE DERIVATIVE; CYTOCHROME P450; MUTANT PROTEIN;

BIOTRANSFORMATION; GENETICS; HYDROXYLATION; METABOLIC ENGINEERING; METABOLISM; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RHODOCOCCUS;

BIOTRANSFORMATION; CYTOCHROME P-450 ENZYME SYSTEM; HYDROXYLATION; MAGNETIC RESONANCE SPECTROSCOPY; METABOLIC ENGINEERING; MUTANT PROTEINS; NORANDROSTANES; RHODOCOCCUS;

EID: 84939964784     PISSN: 01757598     EISSN: 14320614     Source Type: Journal    
DOI: 10.1007/s00253-014-6281-7     Document Type: Article

References (49)

1. Bernhardt R (2006) Cytochromes P450 as versatile biocatalysts. J Biotechnol 124:128–145
2. Bleif S, Hannemann F, Zapp J, Hartmann D, Jauch J, Bernhardt R (2012) A new Bacillus megaterium whole-cell catalyst for the hydroxylation of the pentacyclic triterpene 11-keto-beta-boswellic acid (KBA) based on a recombinant cytochrome P450 system. Appl Microbiol Biotechnol 93:1135–1146
3. Chefson A, Auclair K (2006) Progress towards the easier use of P450 enzymes. Mol Biosyst 2:462–469
4. Clouthier CM, Pelletier JN (2012) Expanding the organic toolbox: a guide to integrating biocatalysis in synthesis. Chem Soc Rev 41:1585–1605
5. Damsten MC, van Vugt-Lussenburg BM, Zeldenthuis T, de Vlieger JS, Commandeur JN, Vermeulen NP (2008) Application of drug metabolising mutants of cytochrome P450 BM3 (CYP102A1) as biocatalysts for the generation of reactive metabolites. Chem Biol Interact 171:96–107
6. de Vlieger JS, Kolkman AJ, Ampt KA, Commandeur JN, Vermeulen NP, Kool J, Wijmenga SS, Niessen WM, Irth H, Honing M (2010) Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR. J Chromatogr B Analyt Technol Biomed Life Sci 878:667–674
7. Donova MV, Egorova OV (2012) Microbial steroid transformations: current state and prospects. Appl Microbiol Biotechnol 94:1423–1447
8. Drăgan CA, Zearo S, Hannemann F, Bernhardt R, Bureik M (2005) Efficient conversion of 11-deoxycortisol to cortisol (hydrocortisone) by recombinant fission yeast Schizosaccharomyces pombe. FEMS Yeast Res 5:621–625
9. Fasan R, Crook NC, Peters MW, Meinhold P, Buelter T, Landwehr M, Cirino PC, Arnold FH (2011) Improved product-per-glucose yields in P450-dependent propane biotransformations using engineered Escherichia coli. Biotechnol Bioeng 108:500–510
10. Gudiminchi RK, Randall C, Opperman DJ, Olaofe OA, Harrison ST, Albertyn J, Smit MS (2012) Whole-cell hydroxylation of n-octane by Escherichia coli strains expressing the CYP153A6 operon. Appl Microbiol Biotechnol 96:1507–1516
11. Hollmann F, Arends IWCE, Buehler K, Schallmey A, Buhler B (2011) Enzyme-mediated oxidations for the chemist. Green Chem 13:226–265
12. Hughes J, Armitage YC, Symes KC (1998) Application of whole cell rhodococcal biocatalysts in acrylic polymer manufacture. Antonie Van Leeuwenhoek 74:107–118
13. Ishige T, Honda K, Shimizu S (2005) Whole organism biocatalysis. Curr Opin Chem Biol 9:174–180
14. Julsing MK, Cornelissen S, Buhler B, Schmid A (2008) Heme-iron oxygenases: powerful industrial biocatalysts? Curr Opin Chem Biol 12:177–186
15. Kille S, Zilly FE, Acevedo JP, Reetz MT (2011) Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution. Nat Chem 3:738–743
16. Kirk DN, Toms HC, Douglas C, White KA, Smith KE, Latif S, Hubbard RWP (1990) A survey of the high-field H-1-NMR spectra of the steroid-hormones, their hydroxylated derivatives, and related-compounds. J Chem Soc Perk T 2:1567–1594
17. 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 410:339–346
18. Kolar NW, Swart AC, Mason JI, Swart P (2007) Functional expression and characterisation of human cytochrome P45017alpha in Pichia pastoris. J Biotechnol 129:635–644
19. Li QS, Ogawa J, Schmid RD, Shimizu S (2001) Engineering cytochrome P450 BM-3 for oxidation of polycyclic aromatic hydrocarbons. Appl Environ Microbiol 67:5735–5739
20. Martinkova L, Uhnakova B, Patek M, Nesvera J, Kren V (2009) Biodegradation potential of the genus Rhodococcus. Environ Int 35:162–177
21. 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 U S A 103:15582–15587
22. Mohn WW, van der Geize R, Stewart GR, Okamoto S, Liu J, Dijkhuizen L, Eltis LD (2008) The actinobacterial mce4 locus encodes a steroid transporter. J Biol Chem 283:35368–35374
23. Munro AW, Leys DG, McLean KJ, Marshall KR, Ost TW, Daff S, Miles CS, Chapman SK, Lysek DA, Moser CC, Page CC, Dutton PL (2002) P450 BM3: the very model of a modern flavocytochrome. Tr Biochem Sci 27:250–257
24. Nakashima N, Tamura T (2004) Isolation and characterization of a rolling-circle-type plasmid from Rhodococcus erythropolis and application of the plasmid to multiple-recombinant-protein expression. Appl Environ Microbiol 70:5557–5568
25. Petric S, Hakki T, Bernhardt R, Zigon D, Cresnar B (2010) Discovery of a steroid 11alpha-hydroxylase from Rhizopus oryzae and its biotechnological application. J Biotechnol 150:428–437
26. Plaggenborg R, Overhage J, Loos A, Archer JA, Lessard P, Sinskey AJ, Steinbuchel A, Priefert H (2006) Potential of Rhodococcus strains for biotechnological vanillin production from ferulic acid and eugenol. Appl Microbiol Biotechnol 72:745–755
27. Quan S, Dabbs ER (1993) Nocardioform arsenic resistance plasmid characterization and improved Rhodococcus cloning vectors. Plasmid 29:74–79
28. Ran N, Zhao L, Chen Z, Tao J (2008) Recent applications of biocatalysis in developing green chemistry for chemical synthesis at the industrial scale. Green Chem 10:361–372
29. Rea V, Kolkman AJ, Vottero E, Stronks EJ, Ampt KA, Honing M, Vermeulen NP, Wijmenga SS, Commandeur JN (2012) Active site substitution A82W improves the regioselectivity of steroid hydroxylation by cytochrome P450 BM3 mutants as rationalized by spin relaxation nuclear magnetic resonance studies. Biochemistry 51:750–760
30. Rosłoniec KZ (2010) Steroid transformation by Rhodococcus strains and bacterial cytochrome P450 enzymes. PhD Dissertation, University of Groningen
31. Schewe H, Holtmann D, Schrader J (2009) P450(BM-3)-catalyzed whole-cell biotransformation of alpha-pinene with recombinant Escherichia coli in an aqueous-organic two-phase system. Appl Microbiol Biotechnol 83:849–857
32. Schmid A, Dordick JS, Hauer B, Kiener A, Wubbolts M, Witholt B (2001) Industrial biocatalysis today and tomorrow. Nature 409:258–268
33. Siriphongphaew A, Pisnupong P, Wongkongkatep J, Inprakhon P, Vangnai AS, Honda K, Ohtake H, Kato J, Ogawa J, Shimizu S, Urlacher VB, Schmid RD, Pongtharangkul T (2012) Development of a whole-cell biocatalyst co-expressing P450 monooxygenase and glucose dehydrogenase for synthesis of epoxyhexane. Appl Microbiol Biotechnol 95:357–367
34. Taguchi K, Motoyama M, Kudo T (2004) Multiplicity of 2,3-dihydroxybiphenyl dioxygenase genes in the Gram-positive polychlorinated biphenyl degrading bacterium Rhodococcus rhodochrous K37. Biosci Biotechnol Biochem 68:787–795
35. Urlacher VB, Girhard M (2011) Cytochrome P450 monooxygenases: an update on perspectives for synthetic application. Tr Biotechnol 30:26–36
36. Urlacher VB, Lutz-Wahl S, Schmid RD (2004) Microbial P450 enzymes in biotechnology. Appl Microbiol Biotechnol 64:317–325
37. van der Geize R, Dijkhuizen L (2004) Harnessing the catabolic diversity of rhodococci for environmental and biotechnological applications. Curr Opin Microbiol 7:255–2261
38. 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 66:2029–2036
39. 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 Delta1-dehydrogenase, in Rhodococcus erythropolis SQ1 using sacB as counter-selectable marker. FEMS Microbiol Lett 205:197–202
40. van der Geize R, Hessels GI, Dijkhuizen L (2002a) Molecular and functional characterization of the kstD2 gene of Rhodococcus erythropolis SQ1 encoding a second 3-ketosteroid Delta (1)-dehydrogenase isoenzyme. Microbiol 148:3285–3292
41. van der Geize R, Hessels GI, van Gerwen R, van der Meijden P, Dijkhuizen L (2002b) Molecular and functional characterization of kshA and kshB, encoding two components of 3-ketosteroid 9alpha-hydroxylase, a class IA monooxygenase, in Rhodococcus erythropolis strain SQ1. Mol Microbiol 45:1007–1018
42. 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 74:7197–7203
43. van Vugt-Lussenburg BM, Stjernschantz E, Lastdrager J, Oostenbrink C, Vermeulen NP, Commandeur JN (2007) Identification of critical residues in novel drug metabolizing mutants of cytochrome P450 BM3 using random mutagenesis. J Med Chem 50:455–461
44. Venkataraman H, Beer SB, Bergen LA, Essen N, Geerke DP, Vermeulen NP, Commandeur JN (2012a) A single active site mutation inverts stereoselectivity of 16-hydroxylation of testosterone catalyzed by engineered cytochrome P450 BM3. Chembiochem 13:520–523
45. Venkataraman H, de Beer SBA, Geerke DP, Vermeulen NPE, Commandeur JNM (2012b) Regio- and stereoselective hydroxylation of optically active α-ionone enantiomers by engineered cytochrome P450 BM3 mutants. Adv Synth Catal 354:2172–2184
46. Whitehouse CJ, Bell SG, Wong LL (2012) P450(BM3) (CYP102A1): connecting the dots. Chem Soc Rev 41:1218–1260
47. Yim SK, Kim DH, Jung HC, Pan JG, Kang HS, Ahn T, Yun CH (2010) Surface display of heme- and diflavin-containing cytochrome P450 BM3 in Escherichia coli: a whole cell biocatalyst for oxidation. J Microbiol Biotechnol 20:712–717
48. Zehentgruber D, Dragan CA, Bureik M, Lutz S (2010a) Challenges of steroid biotransformation with human cytochrome P450 monooxygenase CYP21 using resting cells of recombinant Schizosaccharomyces pombe. J Biotechnol 146:179–185
49. Zehentgruber D, Hannemann F, Bleif S, Bernhardt R, Lutz S (2010b) Towards preparative scale steroid hydroxylation with cytochrome P450 monooxygenase CYP106A2. Chembiochem 11:713–721