A CYP21A2 based whole-cell system in Escherichia coli for the biotechnological production of premedrol

Microbial Cell Factories

Volumn 14, Issue 1, 2015, Pages

  Brixius Anderko, Simone ^a   Schiffer, Lina ^a   Hannemann, Frank ^a   Janocha, Bernd ^b   Bernhardt, Rita ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b SANOFI AVENTIS DEUTSCHLAND GMBH   (Germany)

Author keywords

Adx; Arh1; CPR; CYP21A2; Cytochrome P450; E. coli; Etp1^{fd< sup>; Medrane; Methylprednisolone; Steroid; Whole cell biocatalysis}

Indexed keywords

COMPLEMENTARY DNA; CYTOCHROME P450; CYTOCHROME P450 CYP21A2; PREDNISOLONE DERIVATIVE; PREMEDROL; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE FERRIHEMOPROTEIN REDUCTASE; UNCLASSIFIED DRUG; METHYLPREDNISOLONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE FERRIHEMOPROTEIN REDUCTASE; STEROID 21 MONOOXYGENASE;

ARTICLE; BIOCATALYSIS; BIOREACTOR; BIOTECHNOLOGICAL PRODUCTION; CHEMICAL REACTION; DRUG HYDROXYLATION; DRUG SYNTHESIS; DRUG TRANSFORMATION; ESCHERICHIA COLI; GENE EXPRESSION; NONHUMAN; OXIDATION REDUCTION REACTION; PROCESS OPTIMIZATION; WHOLE CELL; ANIMAL; BIOTRANSFORMATION; BOVINE; GENE VECTOR; GENETICS; METABOLIC ENGINEERING; METABOLISM;

ANIMALS; BIOCATALYSIS; BIOREACTORS; BIOTRANSFORMATION; CATTLE; ESCHERICHIA COLI; GENETIC VECTORS; METABOLIC ENGINEERING; METHYLPREDNISOLONE; NADPH-FERRIHEMOPROTEIN REDUCTASE; OXIDATION-REDUCTION; STEROID 21-HYDROXYLASE;

EID: 84941639570     PISSN: None     EISSN: 14752859     Source Type: Journal    
DOI: 10.1186/s12934-015-0333-2     Document Type: Article

References (53)

1. Flammer JR, Rogatsky I. Minireview: Glucocorticoids in autoimmunity: unexpected targets and mechanisms. Mol Endocrinol. 2011;25:1075-86.
2. Boland EW, Liddle GW. Metabolic and antirheumatic activities of 6-methyl-prednisolone (Medrol). Ann Rheum Dis. 1957;16:297-306.
3. Sambamurthy K, Ashotosh K. Pharmaceutical Biotechnology. New Delhi: New Age International (P) Ltd, Publishers; 2006.
4. Zingler VC, Strupp M, Jahn K, Gross A, Hohlfeld R, Brandt T. The effect of combined mitoxantrone and methylprednisolone therapy in primary and secondary progressive multiple sclerosis. An applied study in 65 patients. Nervenarzt. 2005;76:740-7.
5. Woodward RB, Brutcher FV. cis-Hydroxylation of a synthetic steroid intermediate with iodine, silver acetate and wet acetic acid. J Am Chem Soc. 1958;80:209-11.
6. Schmidlin J, Wettstein A. Synthese Aldosteron-ähnlicher Corticosteroide. d, l-18-Hydroxycorticosteron und d, l-18-Desoxyaldosteron. Helv Chim Acta. 1961;44:1596-607.
7. Boudi A, Lemoine P, Viossat B, Tomas A, Fiet J, Galons H. A convenient synthesis of 18-hydroxycorticosterone and 18-hydroxy-11-desoxycorticosterone via stereospecific hypoiodination of 20-hydroxysteroids. Tetrahedron. 1999;55:5171-6.
8. Ryan KJ, Engel LL. Hydroxylation of steroids at carbon 21. J Biol Chem. 1956;225:103-14.
9. Kominami S, Ochi H, Kobayashi Y, Takemori S. Studies on the steroid hydroxylation system in adrenal cortex microsomes. Purification and characterization of cytochrome P-450 specific for steroid C-21 hydroxylation. J Biol Chem. 1980;255:3386-94.
10. Mizrachi D, Wang Z, Sharma KK, Gupta MK, Xu K, Dwyer CR, Auchus RJ. Why human cytochrome P450c21 is a progesterone 21-hydroxylase. Biochemistry. 2011;50:3968-74.
11. Hubbard PA, Shen AL, Paschke R, Kasper CB, Kim JJ. NADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer. J Biol Chem. 2001;276:29163-70.
12. Hannemann F, Bichet A, Ewen KM, Bernhardt R. Cytochrome P450 systems-biological variations of electron transport chains. Biochim Biophys (BBA) Acta Gen Subj. 2007;1770:330-44.
13. Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes: I. Evidence for its hemoprotein nature. J Biol Chem. 1964;239:2370-8.
14. Bernhardt R. Cytochromes P450 as versatile biocatalysts. J Biotechnol. 2006;124:128-45.
15. Bernhardt R, Urlacher V. Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations. Appl Microbiol Biotechnol. 2014;98:6185-203.
16. Petzoldt KD, Annen KD, Laurent HD.Process for the preparation of 11-beta-hydroxy steroids. Berlin: Schering Aktengesellschaft; 1983.
17. Jänig G-R, Pfeil D, Müller-Frohne M, Riemer H, Henning M, Schwarze W, Ruckpaul K. Steroid 11ß-hydroxylation by a fungal microsomal cytochrome P450. J Steroid Biochem Mol Biol. 1992;43:1117-23.
18. Suzuki K, Sanga K, Chikaoka Y, Itagaki E. Purification and properties of cytochrome P-450 (P-450lun) catalyzing steroid 11 beta-hydroxylation in Curvularia lunata. Biochim Biophys Acta. 1993;8:215-23.
19. Szczebara FM, Chandelier C, Villeret C, Masurel A, Bourot S, Duport C, Blanchard S, Groisillier A, Testet E, Costaglioli P, et al. Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat Biotech. 2003;21:143-9.
20. Schiffer L, Anderko S, Hobler A, Hannemann F, Kagawa N, Bernhardt R. A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale. Microb Cell Fact. 2015;14:25.
21. Schmid A, Dordick JS, Hauer B, Kiener A, Wubbolts M, Witholt B. Industrial biocatalysis today and tomorrow. Nature. 2001;409:258-68.
22. Zehentgruber D, Dragan CA, Bureik M, Lutz S. Challenges of steroid biotransformation with human cytochrome P450 monooxygenase CYP21 using resting cells of recombinant Schizosaccharomyces pombe. J Biotechnol. 2010;146:179-85.
23. Hannemann F, Virus C, Bernhardt R. Design of an Escherichia coli system for whole cell mediated steroid synthesis and molecular evolution of steroid hydroxylases. J Biotechnol. 2006;124:172-81.
24. Arase M, Waterman MR, Kagawa N. Purification and characterization of bovine steroid 21-hydroxylase (P450c21) efficiently expressed in Escherichia coli. Biochem Biophys Res Commun. 2006;344:400-5.
25. Zhao B, Lei L, Kagawa N, Sundaramoorthy M, Banerjee S, Nagy LD, Guengerich FP, Waterman MR. Three-dimensional structure of steroid 21-hydroxylase (cytochrome P450 21A2) with two substrates reveals locations of disease-associated variants. J Biol Chem. 2012;287:10613-22.
26. Nishihara K, Kanemori M, Kitagawa M, Yanagi H, Yura T. Chaperone coexpression plasmids: differential and synergistic roles of DnaK-DnaJ-GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar pollen, Cryj2, in Escherichia coli. Appl Environ Microbiol. 1998;64:1694-9.
27. Ringle M, Khatri Y, Zapp J, Hannemann F, Bernhardt R. Application of a new versatile electron transfer system for cytochrome P450-based Escherichia coli whole-cell bioconversions. Appl Microbiol Biotechnol. 2013;97:7741-54.
28. Girhard M, Klaus T, Khatri Y, Bernhardt R, Urlacher VB. Characterization of the versatile monooxygenase CYP109B1 from Bacillus subtilis. Appl Microbiol Biotechnol. 2010;87:595-607.
29. Walton AZ, Stewart JD. Understanding and Improving NADPH-dependent reactions by nongrowing Escherichia coli Cells. Biotechnol Prog. 2004;20:403-11.
30. Lambeth JD, Seybert DW, Lancaster JR, Salerno JC, Kamin H. Steroidogenic electron transport in adrenal cortex mitochondria. Mol Cell Biochem. 1982;45:13-31.
31. Ewen KM, Kleser M, Bernhardt R. Adrenodoxin: The archetype of vertebrate-type [2Fe-2S] cluster ferredoxins. Biochim Biophys Acta (BBA) Gen Subj. 2011;1814:111-25.
32. Ewen KM, Ringle M, Bernhardt R. Adrenodoxin-A versatile ferredoxin. IUBMB Life. 2012;64:506-12.
33. Pechurskaya TA, Harnastai IN, Grabovec IP, Gilep AA, Usanov SA. Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s. Biochem Biophys Res Commun. 2007;353:598-604.
34. Uhlmann H, Kraft R, Bernhardt R. C-terminal region of adrenodoxin affects its structural integrity and determines differences in its electron transfer function to cytochrome P-450. J Biol Chem. 1994;269:22557-64.
35. P-r Cao, Bernhardt R. Modulation of aldosterone biosynthesis by adrenodoxin mutants with different electron transport efficiencies. Eur J Biochem. 1999;265:152-9.
36. Ewen KM, Schiffler B, Uhlmann-Schiffler H, Bernhardt R, Hannemann F. The endogenous adrenodoxin reductase-like flavoprotein arh1 supports heterologous cytochrome P450-dependent substrate conversions in Schizosaccharomyces pombe. FEMS Yeast Res. 2008;8:432-41.
37. Barros MH, Nobrega FG, Tzagoloff A. Mitochondrial ferredoxin is required for heme A synthesis in Saccharomyces cerevisiae. J Biol Chem. 2002;277:9997-10002.
38. Bureik M, Schiffler B, Hiraoka Y, Vogel F, Bernhardt R. Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1†. Biochemistry. 2002;41:2311-21.
39. Schiffler B, Bureik M, Reinle W, Muller EC, Hannemann F, Bernhardt R. The adrenodoxin-like ferredoxin of Schizosaccharomyces pombe mitochondria. J Inorg Biochem. 2004;98:1229-37.
40. Lacour T, Achstetter T, Dumas B. Characterization of recombinant adrenodoxin reductase homologue (Arh1p) from yeast: implication in in vitro cytochrome P45011β monooxygenase system. J Biol Chem. 1998;273:23984-92.
41. Janocha S, Bernhardt R. Design and characterization of an efficient CYP105A1-based whole-cell biocatalyst for the conversion of resin acid diterpenoids in permeabilized Escherichia coli. Appl Microbiol Biotechnol. 2013;97:7639-49.
42. McIver L, Leadbeater C, Campopiano DJ, Baxter RL, Daff SN, Chapman SK, Munro AW. Characterisation of flavodoxin NADP+ oxidoreductase and flavodoxin; key components of electron transfer in Escherichia coli. Eur J Biochem. 1998;257:577-85.
43. Jenkins CM, Waterman MR. NADPH- flavodoxin reductase and flavodoxin from Escherichia coli: characteristics as a soluble microsomal P450 reductase. Biochemistry. 1998;37:6106-13.
44. Tseng H-C, Martin CH, Nielsen DR, Prather KLJ. Metabolic engineering of Escherichia coli for enhanced production of (R)- and (S)-3-hydroxybutyrate. Appl Environ Microbiol. 2009;75:3137-45.
45. Brumaghim JL, Li Y, Henle E, Linn S. Effects of hydrogen peroxide upon nicotinamide nucleotide metabolism in Escherichia coli: changes in enzyme levels and nicotinamide nucleotide pools and studies of the oxidation of NAD(P)H by Fe(III). J Biol Chem. 2003;278:42495-504.
46. Hernández-Martín A, von Bühler CJ, Tieves F, Fernández S, Ferrero M, Urlacher VB. Whole-cell biotransformation with recombinant cytochrome P450 for the selective oxidation of Grundmann's ketone. Bioorganic Med Chem. 2014;22:5586-92.
47. Miroux B, Walker JE. Over-production of proteins in Escherichia coli: mutant hosts that allow synthesis of some membrane proteins and globular proteins at high levels. J Mol Biol. 1996;260:289-98.
48. von Wachenfeldt C, Richardson TH, Cosme J, Johnson EF. Microsomal P450 2C3 is expressed as a soluble dimer in Escherichia coli following modifications of its N-terminus. Arch Biochem Biophys. 1997;339:107-14.
49. Neunzig J, Sánchez-Guijo A, Mosa A, Hartmann MF, Geyer J, Wudy SA, Bernhardt R. A steroidogenic pathway for sulfonated steroids: the metabolism of pregnenolone sulfate. J Steroid Biochem Mol Biol. 2014;144(Part B):324-33.
50. Sagara Y, Wada A, Takata Y, Waterman MR, Sekimizu K, Horiuchi T. Direct expression of adrenodoxin reductase in Escherichia coli and the functional characterization. Biol Pharm Bull. 1993;16:627-30.
51. Khatri Y, Girhard M, Romankiewicz A, Ringle M, Hannemann F, Urlacher V, Hutter M, Bernhardt R. Regioselective hydroxylation of norisoprenoids by CYP109D1 from Sorangium cellulosum So ce56. Appl Microbiol Biotechnol. 2010;88:485-95.
52. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680-5.
53. Renart J, Reiser J, Stark GR. Transfer of proteins from gels to diazobenzyloxymethyl-paper and detection with antisera: a method for studying antibody specificity and antigen structure. Proc Natl Acad Sci USA. 1979;76:3116-20.