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Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations

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Abstract

Cytochromes P450 (CYPs) belong to the superfamily of heme b containing monooxygenases with currently more than 21,000 members. These enzymes accept a vast range of organic molecules and catalyze diverse reactions. These extraordinary capabilities of CYP systems that are unmet by other enzymes make them attractive for biotechnology. However, the complexity of these systems due to the need of electron transfer from nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) via redox partner proteins for the initial hydroxylation step limits a broader technical implementation of CYP enzymes. There have been several reviews during the past years tackling the potential CYPs for synthetic application. The aim of this review is to give a critical overview about possibilities and chances for application of these interesting catalysts as well as to discuss drawbacks and problems related to their use. Solutions to overcome these limitations will be demonstrated, and several selected examples of successful CYP applications under industrial conditions will be reviewed.

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References

  • Abokitse K, Hummel W (2003) Cloning, sequence analysis, and heterologous expression of the gene encoding a (S)-specific alcohol dehydrogenase from Rhodococcus erythropolis DSM 43297. Appl Microbiol Biotechnol 62:380–386

  • Ahmed F, Al-Mutairi EH, Avery KL, Cullis PM, Primrose WU, Roberts GCK, Willis CL (1999) An unusual matrix of stereocomplementarity in the hydroxylation of monohydroxy fatty acids catalysed by cytochrome P-450 from Bacillus megaterium with potential application in biotransformations. Chem Commun (Camb):2049-2050

  • Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330:70–74

    CAS  PubMed Central  PubMed  Google Scholar 

  • Andreadeli A, Platis D, Tishkov V, Popov V, Labrou NE (2008) Structure-guided alteration of coenzyme specificity of formate dehydrogenase by saturation mutagenesis to enable efficient utilization of NADP+. FEBS J 275:3859–3869

    CAS  PubMed  Google Scholar 

  • Arai M, Serizawa N, Terahara A, Tsujita Y, Tanaka M, Masuda H, Ishikawa S (1988) Pravastatin sodium (CS-514), a novel cholesterol-lowering agent which inhibits HMG-CoA reductase. Sankyo Kenkyusyo Nenpo 40:1–38

    CAS  Google Scholar 

  • Ba L, Li P, Zhang H, Duan Y, Lin Z (2013) Semi-rational engineering of cytochrome P450sca-2 in a hybrid system for enhanced catalytic activity: insights into the important role of electron transfer. Biotechnol Bioeng 110:2815–2825

    CAS  PubMed  Google Scholar 

  • Barry SM, Kers JA, Johnson EG, Song L, Aston PR, Patel B, Krasnoff SB, Crane BR, Gibson DM, Loria R, Challis GL (2012) Cytochrome P450-catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat Chem Biol 8:814–816

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beckert V, Dettmer R, Bernhardt R (1994) Mutations of tyrosine 82 in bovine adrenodoxin that affect binding to cytochromes P45011A1 and P45011B1 but not electron transfer. J Biol Chem 269:2568–2573

    CAS  PubMed  Google Scholar 

  • Bell SG, Dale A, Rees NH, Wong LL (2010a) A cytochrome P450 class I electron transfer system from Novosphingobium aromaticivorans. Appl Microbiol Biotechnol 86:163–175

    CAS  PubMed  Google Scholar 

  • Bell SG, Xu F, Johnson EO, Forward IM, Bartlam M, Rao Z, Wong LL (2010b) Protein recognition in ferredoxin-P450 electron transfer in the class I CYP199A2 system from Rhodopseudomonas palustris. J Biol Inorg Chem 15:315–328

    CAS  PubMed  Google Scholar 

  • Bell SG, McMillan JH, Yorke JA, Kavanagh E, Johnson EO, Wong LL (2012) Tailoring an alien ferredoxin to support native-like P450 monooxygenase activity. Chem Commun (Camb) 48:11692–11694

    CAS  Google Scholar 

  • Bell SG, French L, Rees NH, Cheng SS, Preston G, Wong LL (2013) A phthalate family oxygenase reductase supports terpene alcohol oxidation by CYP238A1 from Pseudomonas putida KT2440. Biotechnol Appl Biochem 60:9–17

    CAS  PubMed  Google Scholar 

  • Berg A, Ingelman-Sundberg M, Gustafsson JA (1979) Purification and characterization of cytochrome P-450meg. J Biol Chem 254:5264–5271

    CAS  PubMed  Google Scholar 

  • Bernhardt R (1996) Cytochrome P450: structure, function, and generation of reactive oxygen species. Rev Physiol Biochem Pharmacol 127:137–221

    CAS  PubMed  Google Scholar 

  • Bernhardt R (2000) The role of adrenodoxin in adrenal steroidogenesis. Curr Opin Endocrinol Diabetes 7:109–115

    CAS  Google Scholar 

  • Bernhardt R (2004) Cytochrome P-450. In: Lennarz WJ, Lane MD (eds) Encyclopedia of biological chemistry, edn. Elsevier, New York, pp 544–549

    Google Scholar 

  • Bernhardt R (2006) Cytochromes P450 as versatile biocatalysts. J Biotechnol 124:128–145

    CAS  PubMed  Google Scholar 

  • Bernhardt R (2013) Cytochrome P450. In: Lennarz WJ, Lane MD (eds) The encyclopedia of biological chemistry, edn. Academic Press, Waltham, pp 607–612

    Google Scholar 

  • Bernhardt R, Waterman MR (2007) Cytochrome P450 and steroid hormone biosynthesis. In: Sigel A, Sigel H, Sigel RKO (eds) The ubiquitous roles of cytochrome P450 proteins, edn. Wiley, Chichester, pp 361–369

    Google Scholar 

  • Bleif S, Hannemann F, Lisurek M, von Kries JP, Zapp J, Dietzen M, Antes I, Bernhardt R (2011) Identification of CYP106A2 as a regioselective allylic bacterial diterpene hydroxylase. Chembiochem 12:576–582

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Boerma JS, Vermeulen NP, Commandeur JN (2011) Application of CYP102A1M11H as a tool for the generation of protein adducts of reactive drug metabolites. Chem Res Toxicol 24:1263–1274

    CAS  PubMed  Google Scholar 

  • Brill E, Hannemann F, Zapp J, Bruning G, Jauch J, Bernhardt R (2013) A new cytochrome P450 system from Bacillus megaterium DSM319 for the hydroxylation of 11-keto-beta-boswellic acid (KBA). Appl Microbiol Biotechnol 25. doi:10.1007/s00253-00013-05029-00250

  • Cao PR, Bernhardt R (1999) Modulation of aldosterone biosynthesis by adrenodoxin mutants with different electron transport efficiencies. Eur J Biochem 265:152–159

    CAS  PubMed  Google Scholar 

  • Cao PR, Bulow H, Dumas B, Bernhardt R (2000) Construction and characterization of a catalytic fusion protein system: P-450(11beta)-adrenodoxin reductase-adrenodoxin. Biochim Biophys Acta 1476:253–264

    CAS  PubMed  Google Scholar 

  • Carballeira JD, Quezada MA, Hoyos P, Simeo Y, Hernaiz MJ, Alcantara AR, Sinisterra JV (2009) Microbial cells as catalysts for stereoselective red-ox reactions. Biotechnol Adv 27:686–714

    CAS  PubMed  Google Scholar 

  • Chen CH, Hu HY, Cho YC, Hsu WH (2006) Screening of compactin-resistant microorganisms capable of converting compactin to pravastatin. Curr Microbiol 53:108–112

    CAS  PubMed  Google Scholar 

  • Chun YJ, Shimada T, Waterman MR, Guengerich FP (2006) Understanding electron transport systems of Streptomyces cytochrome P450. Biochem Soc Trans 34:1183–1185

    CAS  PubMed  Google Scholar 

  • Chun YJ, Shimada T, Sanchez-Ponce R, Martin MV, Lei L, Zhao B, Kelly SL, Waterman MR, Lamb DC, Guengerich FP (2007) Electron transport pathway for a Streptomyces cytochrome P450: cytochrome P450 105D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2). J Biol Chem 282:17486–17500

    CAS  PubMed  Google Scholar 

  • Cirino PC, Arnold FH (2003) A self-sufficient peroxide-driven hydroxylation biocatalyst. Angew Chem Int Ed Engl 42:3299–3301

    CAS  PubMed  Google Scholar 

  • Cirino PC, Tang Y, Takahashi K, Tirrell DA, Arnold FH (2003) Global incorporation of norleucine in place of methionine in cytochrome P450 BM-3 heme domain increases peroxygenase activity. Biotechnol Bioeng 83:729–734

    CAS  PubMed  Google Scholar 

  • Coelho PS, Brustad EM, Kannan A, Arnold FH (2013a) Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science 339:307–310

    CAS  PubMed  Google Scholar 

  • Coelho PS, Wang ZJ, Ener ME, Baril SA, Kannan A, Arnold FH, Brustad EM (2013b) A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo. Nat Chem Biol 9:485–487

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cornelissen S, Julsing MK, Volmer J, Riechert O, Schmid A, Buhler B (2013) Whole-cell-based CYP153A6-catalyzed (S)-limonene hydroxylation efficiency depends on host background and profits from monoterpene uptake via AlkL. Biotechnol Bioeng 110:1282–1292

  • De Mot R, Parret AH (2002) A novel class of self-sufficient cytochrome P450 monooxygenases in prokaryotes. Trends Microbiol 10:502–508

    PubMed  Google Scholar 

  • Denisov IG, Sligar SG (2011) Cytochromes P450 in nanodiscs. Biochim Biophys Acta 1814:223–229

    CAS  PubMed Central  PubMed  Google Scholar 

  • Di Nardo G, Gilardi G (2012) Optimization of the bacterial cytochrome P450 BM3 system for the production of human drug metabolites. Int J Mol Sci 13:15901–15924

    PubMed Central  PubMed  Google Scholar 

  • Dingler C, Ladner W, Krei GA, Cooper B, Hauer B (1996) Preparation of (R)-2-(4-hydroxyphenoxy) propionic acid by biotransformation. Pestic Sci 46:33–35

  • Donova MV, Egorova OV (2012) Microbial steroid transformations: current state and prospects. Appl Microbiol Biotechnol 94:1423–1447

    CAS  PubMed  Google Scholar 

  • Donova MV, Nikolayeva VM, Dovbnya DV, Gulevskaya SA, Suzina NE (2007) Methyl-beta-cyclodextrin alters growth, activity and cell envelope features of sterol-transforming mycobacteria. Microbiology 153:1981–1992

    CAS  PubMed  Google Scholar 

  • Dragan CA, Blank LM, Bureik M (2006) Increased TCA cycle activity and reduced oxygen consumption during cytochrome P450-dependent biotransformation in fission yeast. Yeast 23:779–794

    CAS  PubMed  Google Scholar 

  • Duport C, Spagnoli R, Degryse E, Pompon D (1998) Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast. Nat Biotechnol 16:186–189

    CAS  PubMed  Google Scholar 

  • Estabrook RW, Shet MS, Fisher CW, Jenkins CM, Waterman MR (1996) The interaction of NADPH-P450 reductase with P450: an electrochemical study of the role of the flavin mononucleotide-binding domain. Arch Biochem Biophys 333:308–315

    CAS  PubMed  Google Scholar 

  • Ewen KM, Kleser M, Bernhardt R (2010) Adrenodoxin: the archetype of vertebrate-type [2Fe-2S] cluster ferredoxins. Biochim Biophys Acta:111-125

  • Ewen KM, Hannemann F, Iametti S, Morleo A, Bernhardt R (2011) Functional characterization of Fdx1: evidence for an evolutionary relationship between P450-type and ISC-type ferredoxins. J Mol Biol 413:940–951

    CAS  PubMed  Google Scholar 

  • Ewen KM, Ringle M, Bernhardt R (2012) Adrenodoxin—a versatile ferredoxin. IUBMB Life 64:506–512

    CAS  PubMed  Google Scholar 

  • Falck JR, Reddy YK, Haines DC, Reddy KM, Krishna UM, Graham S, Murry B, Peterson JA (2001) Practical, enantiospecific synthesis of 14,15-EET and leukotoxin B (vernolic acid). Tetrahedron Lett 42:4131–4133

    CAS  Google Scholar 

  • Fantuzzi A, Capria E, Mak LH, Dodhia VR, Sadeghi SJ, Collins S, Somers G, Huq E, Gilardi G (2010) An electrochemical microfluidic platform for human P450 drug metabolism profiling. Anal Chem 82:10222–10227

    CAS  PubMed  Google Scholar 

  • Fantuzzi A, Mak LH, Capria E, Dodhia V, Panicco P, Collins S, Gilardi G (2011) A new standardized electrochemical array for drug metabolic profiling with human cytochromes P450. Anal Chem 83:3831–3839

    CAS  PubMed  Google Scholar 

  • Faro M, Schiffler B, Heinz A, Nogues I, Medina M, Bernhardt R, Gomez-Moreno C (2003) Insights into the design of a hybrid system between Anabaena ferredoxin-NADP+ reductase and bovine adrenodoxin. Eur J Biochem 270:726–735

  • Fasan R, Chen MM, Crook NC, Arnold FH (2007) Engineered alkane-hydroxylating cytochrome P450(BM3) exhibiting nativelike catalytic properties. Angew Chem Int Ed Engl 46:8414–8418

    CAS  PubMed  Google Scholar 

  • Fasan R, Meharenna YT, Snow CD, Poulos TL, Arnold FH (2008) Evolutionary history of a specialized P450 propane monooxygenase. J Mol Biol 383:1069–1080

  • Ferrero VE, Andolfi L, Di Nardo G, Sadeghi SJ, Fantuzzi A, Cannistraro S, Gilardi G (2008) Protein and electrode engineering for the covalent immobilization of P450 BMP on gold. Anal Chem 80:8438–8446

    CAS  PubMed  Google Scholar 

  • Fleming BD, Johnson DL, Bond AM, Martin LL (2006) Recent progress in cytochrome P450 enzyme electrochemistry. Expert Opin Drug Metab Toxicol 2:581–589

    CAS  PubMed  Google Scholar 

  • Forkmann G, Martens S (2001) Metabolic engineering and applications of flavonoids. Curr Opin Biotechnol 12:155–160

    CAS  PubMed  Google Scholar 

  • Fujii T, Fujii Y, Machida K, Ochiai A, Ito M (2009) Efficient biotransformations using Escherichia coli with tolC acrAB mutations expressing cytochrome P450 genes. Biosci Biotechnol Biochem 73:805–810

    CAS  PubMed  Google Scholar 

  • Fujishiroa T, Shoji O, Watanabe Y (2010) Non-covalent modification of the active site of cytochrome P450 for inverting the stereoselectivity of monooxygenation. Tetrahedron Lett 52:395–397

    Google Scholar 

  • Fulco AJ (1991) P450BM-3 and other inducible bacterial P450 cytochromes: biochemistry and regulation. Annu Rev Pharmacol Toxicol 31:177–203

    CAS  PubMed  Google Scholar 

  • Gavira C, Hofer R, Lesot A, Lambert F, Zucca J, Werck-Reichhart D (2013) Challenges and pitfalls of P450-dependent (+)-valencene bioconversion by Saccharomyces cerevisiae. Metab Eng 18:25–35

    CAS  PubMed  Google Scholar 

  • Gerber NC, Sligar SG (1994) A role for Asp251 in cytochrome P-450cam oxygen activation. J Biol Chem 269:4260–4266

    CAS  PubMed  Google Scholar 

  • Gillam EM (2007) Extending the capabilities of nature’s most versatile catalysts: directed evolution of mammalian xenobiotic-metabolizing P450s. Arch Biochem Biophys 464:176–186

    CAS  PubMed  Google Scholar 

  • Gillam EM (2008) Engineering cytochrome P450 enzymes. Chem Res Toxicol 21:220–231

    PubMed  Google Scholar 

  • Gillam EM, Guengerich FP (2001) Exploiting the versatility of human cytochrome P450 enzymes: the promise of blue roses from biotechnology. IUBMB Life 52:271–277

    CAS  PubMed  Google Scholar 

  • Girhard M, Schuster S, Dietrich M, Durre P, Urlacher VB (2007) Cytochrome P450 monooxygenase from Clostridium acetobutylicum: a new alpha-fatty acid hydroxylase. Biochem Biophys Res Commun 362:114–119

    CAS  PubMed  Google Scholar 

  • Girhard M, Machida K, Itoh M, Schmid RD, Arisawa A, Urlacher VB (2009) Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing CYP109B1 from Bacillus subtilis in a two-liquid-phase system. Microb Cell Factories 8(36):1–13

  • Girhard M, Klaus T, Khatri Y, Bernhardt R, Urlacher VB (2010) Characterization of the versatile monooxygenase CYP109B1 from Bacillus subtilis. Appl Microbiol Biotechnol 87:595–607

    CAS  PubMed  Google Scholar 

  • Girhard M, Kunigk E, Tihovsky S, Shumyantseva VV, Urlacher VB (2013a) Light-driven biocatalysis with cytochrome P450 peroxygenases. Biotechnol Appl Biochem 60:111–118

    CAS  PubMed  Google Scholar 

  • Girhard M, Tieves F, Weber E, Smit MS, Urlacher VB (2013b) Cytochrome P450 reductase from Candida apicola: versatile redox partner for bacterial P450s. Appl Microbiol Biotechnol 97:1625–1635

    CAS  PubMed  Google Scholar 

  • Goni G, Zollner A, Lisurek M, Velazquez-Campoy A, Pinto S, Gomez-Moreno C, Hannemann F, Bernhardt R, Medina M (2009) Cyanobacterial electron carrier proteins as electron donors to CYP106A2 from Bacillus megaterium ATCC 13368. Biochim Biophys Acta 1794:1635–1642

    CAS  PubMed  Google Scholar 

  • Grinkova YV, Denisov IG, Sligar SG (2010) Functional reconstitution of monomeric CYP3A4 with multiple cytochrome P450 reductase molecules in Nanodiscs. Biochem Biophys Res Commun 398:194–198

    CAS  PubMed  Google Scholar 

  • Grinkova YV, Denisov IG, McLean MA, Sligar SG (2013) Oxidase uncoupling in heme monooxygenases: human cytochrome P450 CYP3A4 in Nanodiscs. Biochem Biophys Res Commun 430:1223–1227

    CAS  PubMed  Google Scholar 

  • Guengerich FP, Munro AW (2013) Unusual cytochrome P450 enzymes and reactions. J Biol Chem 288:17065–17073

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haga T, Hirakawa H, Nagamune T (2013) Fine tuning of spatial arrangement of enzymes in a PCNA-mediated multienzyme complex using a rigid poly-L-proline linker. PLoS One 8:1–11

    Google Scholar 

  • Hakki T, Zearo S, Dragan CA, Bureik M, Bernhardt R (2008) Coexpression of redox partners increases the hydrocortisone (cortisol) production efficiency in CYP11B1 expressing fission yeast Schizosaccharomyces pombe. J Biotechnol 133:351–359

    CAS  PubMed  Google Scholar 

  • Hannemann F, Bichet A, Ewen KM, Bernhardt R (2007) Cytochrome P450 systems—biological variations of electron transport chains. Biochim Biophys Acta 1770:330–344

    CAS  PubMed  Google Scholar 

  • Hayashi K, Sugimoto H, Shinkyo R, Yamada M, Ikeda S, Ikushiro S, Kamakura M, Shiro Y, Sakaki T (2008) Structure-based design of a highly active vitamin D hydroxylase from Streptomyces griseolus CYP105A1. Biochemistry 47:11964–11972

    CAS  PubMed  Google Scholar 

  • Hayashi K, Yasuda K, Sugimoto H, Ikushiro S, Kamakura M, Kittaka A, Horst RL, Chen TC, Ohta M, Shiro Y, Sakaki T (2010) Three-step hydroxylation of vitamin D3 by a genetically engineered CYP105A1: enzymes and catalysis. FEBS J 277:3999–4009

    CAS  PubMed  Google Scholar 

  • Hirakawa H, Nagamune T (2010) Molecular assembly of P450 with ferredoxin and ferredoxin reductase by fusion to PCNA. Chembiochem 11:1517–1520

    CAS  PubMed  Google Scholar 

  • Hirakawa H, Kamiya N, Tanaka T, Nagamune T (2007) Intramolecular electron transfer in a cytochrome P450cam system with a site-specific branched structure. Protein Eng Des Sel 20:453–459

    CAS  PubMed  Google Scholar 

  • Hlavica P (2009) Assembly of non-natural electron transfer conduits in the cytochrome P450 system: a critical assessment and update of artificial redox constructs amenable to exploitation in biotechnological areas. Biotechnol Adv 27:103–121

    CAS  PubMed  Google Scholar 

  • Hogg JA (1992) Steroids, the steroid community, and Upjohn in perspective: a profile of innovation. Steroids 57:593–616

    CAS  PubMed  Google Scholar 

  • Holton TA, Brugliera F, Lester DR, Tanaka Y, Hyland CD, Menting JG, Lu CY, Farcy E, Stevenson TW, Cornish EC (1993) Cloning and expression of cytochrome P450 genes controlling flower colour. Nature 366:276–279

    CAS  PubMed  Google Scholar 

  • Hosobuchi M, Kurosawa K, Yoshikawa H (1993) Application of computer to monitoring and control of fermentation process: microbial conversion of ML-236B Na to pravastatin. Biotechnol Bioeng 42:815–820

    CAS  PubMed  Google Scholar 

  • Hotze M, Schroder G, Schroder J (1995) Cinnamate 4-hydroxylase from Catharanthus roseus, and a strategy for the functional expression of plant cytochrome P450 proteins as translational fusions with P450 reductase in Escherichia coli. FEBS Lett 374:345–350

    CAS  PubMed  Google Scholar 

  • Hrycay EG, Bandiera SM (2012) The monooxygenase, peroxidase, and peroxygenase properties of cytochrome P450. Arch Biochem Biophys 522:71–89

    CAS  PubMed  Google Scholar 

  • Imai Y, Matsunaga I, Kusunose E, Ichihara K (2000) Unique heme environment at the putative distal region of hydrogen peroxide-dependent fatty acid alpha-hydroxylase from Sphingomonas paucimobilis (peroxygenase P450(SPalpha). J Biochem 128:189–194

    CAS  PubMed  Google Scholar 

  • Iwuoha EI, Joseph S, Zhang Z, Smyth MR, Fuhr U, Ortiz de Montellano PR (1998) Drug metabolism biosensors: electrochemical reactivities of cytochrome P450cam immobilised in synthetic vesicular systems. J Pharm Biomed Anal 17:1101–1110

    CAS  PubMed  Google Scholar 

  • Jackson CJ, Lamb DC, Marczylo TH, Warrilow AG, Manning NJ, Lowe DJ, Kelly DE, Kelly SL (2002) A novel sterol 14alpha-demethylase/ferredoxin fusion protein (MCCYP51FX) from Methylococcus capsulatus represents a new class of the cytochrome P450 superfamily. J Biol Chem 277:46959–46965

    CAS  PubMed  Google Scholar 

  • Janocha S, Bernhardt R (2013) 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 97:7639–7649

    CAS  PubMed  Google Scholar 

  • Jenkins CM, Waterman MR (1998) NADPH-flavodoxin reductase and flavodoxin from Escherichia coli: characteristics as a soluble microsomal P450 reductase. Biochemistry 37:6106–6113

    CAS  PubMed  Google Scholar 

  • Jennewein S, Long RM, Williams RM, Croteau R (2004) Cytochrome P450 taxadiene 5alpha-hydroxylase, a mechanistically unusual monooxygenase catalyzing the first oxygenation step of taxol biosynthesis. Chem Biol 11:379–387

    CAS  PubMed  Google Scholar 

  • Jensen K, Jensen PE, Moller BL (2011) Light-driven cytochrome P450 hydroxylations. ACS Chem Biol 6:533–539

    CAS  PubMed  Google Scholar 

  • Jensen K, Jensen PE, Moller BL (2012a) Light-driven chemical synthesis. Trends Plant Sci 17:60–63

    CAS  PubMed  Google Scholar 

  • Jensen K, Johnston JB, de Montellano PR, Moller BL (2012b) Photosystem I from plants as a bacterial cytochrome P450 surrogate electron donor: terminal hydroxylation of branched hydrocarbon chains. Biotechnol Lett 34:239–245

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231

    CAS  PubMed  Google Scholar 

  • Joseph S, Rusling JF, Lvov YM, Friedberg T, Fuhr U (2003) An amperometric biosensor with human CYP3A4 as a novel drug screening tool. Biochem Pharmacol 65:1817–1826

    CAS  PubMed  Google Scholar 

  • Julsing MK, Cornelissen S, Buhler B, Schmid A (2008) Heme-iron oxygenases: powerful industrial biocatalysts? Curr Opin Chem Biol 12:177–186

    CAS  PubMed  Google Scholar 

  • Julsing MK, Schrewe M, Cornelissen S, Hermann I, Schmid A, Buhler B (2012) Outer membrane protein AlkL boosts biocatalytic oxyfunctionalization of hydrophobic substrates in Escherichia coli. Appl Environ Microbiol 78:5724–5733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jung ST, Lauchli R, Arnold FH (2011) Cytochrome P450: taming a wild type enzyme. Curr Opin Biotechnol 22:809–817

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kametani T, Furuyama H (1987) Synthesis of vitamin D3 and related compounds. Med Res Rev 7:147–171

    CAS  PubMed  Google Scholar 

  • Katsumoto Y, Fukuchi-Mizutani M, Fukui Y, Brugliera F, Holton TA, Karan M, Nakamura N, Yonekura-Sakakibara K, Togami J, Pigeaire A, Tao GQ, Nehra NS, Lu CY, Dyson BK, Tsuda S, Ashikari T, Kusumi T, Mason JG, Tanaka Y (2007) Engineering of the rose flavonoid biosynthetic pathway successfully generated blue-hued flowers accumulating delphinidin. Plant Cell Physiol 48:1589–1600

    CAS  PubMed  Google Scholar 

  • Khatri Y, Girhard M, Romankiewicz A, Ringle M, Hannemann F, Urlacher VB, Hutter MC, Bernhardt R (2010a) Regioselective hydroxylation of norisoprenoids by CYP109D1 from Sorangium cellulosum So ce56. Appl Microbiol Biotechnol 88:485–495

    CAS  PubMed  Google Scholar 

  • Khatri Y, Hannemann F, Ewen KM, Pistorius D, Perlova O, Kagawa N, Brachmann AO, Muller R, Bernhardt R (2010b) The CYPome of Sorangium cellulosum So ce56 and identification of CYP109D1 as a new fatty acid hydroxylase. Chem Biol 17:1295–1305

    CAS  PubMed  Google Scholar 

  • Kitahama Y, Nakamura M, Yoshida Y, Aoyama Y (2009) The construction and characterization of self-sufficient lanosterol 14-demethylase fusion proteins consisting of yeast CYP51 and its reductase. Biol Pharm Bull 32:558–563

    CAS  PubMed  Google Scholar 

  • Kitazume T, Takaya N, Nakayama N, Shoun H (2000) Fusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome P450BM3. J Biol Chem 275:39734–39740

  • Kleser M, Hannemann F, Hutter M, Zapp J, Bernhardt R (2012) CYP105A1 mediated 3-hydroxylation of glimepiride and glibenclamide using a recombinant Bacillus megaterium whole-cell catalyst. J Biotechnol 157:405–412

    CAS  PubMed  Google Scholar 

  • Koschorreck K, von Bühler CJ, Schulz S, Urlacher VB (2012) Protein engineering of cytochrome P450 monooxygenases. In: Lutz S, Bornscheuer UT (eds) Protein engineering handbook, 1st edn. Wiley-VCH, Weinheim, pp 327–362

    Google Scholar 

  • Kubo T, Peters MW, Meinhold P, Arnold FH (2006) Enantioselective epoxidation of terminal alkenes to (R)- and (S)-epoxides by engineered cytochromes P450 BM-3. Chemistry (Easton) 12:1216–1220

  • Kuehnel K, Maurer SC, Galeyeva Y, Frey W, Laschat S, Urlacher VB (2007) Hydroxylation of dodecanoic acid and (2R,4R,6R,8R)-tetramethyldecanol on a preparative scale using an NADH-dependent CYP102A1 mutant. Adv Synth Catal 349:1451–1461

  • Kumar S, Halpert JR (2005) Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. Biochem Biophys Res Commun 338:456–464

    CAS  PubMed  Google Scholar 

  • Lawson RJ, von Wachenfeldt C, Haq I, Perkins J, Munro AW (2004) Expression and characterization of the two flavodoxin proteins of Bacillus subtilis, YkuN and YkuP: biophysical properties and interactions with cytochrome P450 BioI. Biochemistry 43:12390–12409

    CAS  PubMed  Google Scholar 

  • Lewis JC, Arnold FH (2009) Catalysts on demand: selective oxidations by laboratory-evolved cytochrome P450 BM3. Chimia 63:309–312

    CAS  Google Scholar 

  • Li S, Podust LM, Sherman DH (2007) Engineering and analysis of a self-sufficient biosynthetic cytochrome P450 PikC fused to the RhFRED reductase domain. J Am Chem Soc 129:12940–12941

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lisurek M, Simgen B, Antes I, Bernhardt R (2008) Theoretical and experimental evaluation of a CYP106A2 low homology model and production of mutants with changed activity and selectivity of hydroxylation. Chembiochem 9:1439–1449

    CAS  PubMed  Google Scholar 

  • Luthra A, Gregory M, Grinkova YV, Denisov IG, Sligar SG (2013) Nanodiscs in the studies of membrane-bound cytochrome P450 enzymes. Methods Mol Biol 987(115–27):115–127

    CAS  PubMed  Google Scholar 

  • Makino T, Otomatsu T, Shindo K, Kitamura E, Sandmann G, Harada H, Misawa N (2012) Biocatalytic synthesis of flavones and hydroxyl-small molecules by recombinant Escherichia coli cells expressing the cyanobacterial CYP110E1 gene. Microb Cell Factories 11(95):1–13

    Google Scholar 

  • Makris TM, Davydov R, Denisov IG, Hoffman BM, Sligar SG (2002) Mechanistic enzymology of oxygen activation by the cytochromes P450. Drug Metab Rev 34:691–708

    CAS  PubMed  Google Scholar 

  • Malca SH, Girhard M, Schuster S, Durre P, Urlacher VB (2011) Expression, purification and characterization of two Clostridium acetobutylicum flavodoxins: potential electron transfer partners for CYP152A2. Biochim Biophys Acta 1814:257–264

    PubMed  Google Scholar 

  • Matsunaga I, Yokotani N, Gotoh O, Kusunose E, Yamada M, Ichihara K (1997) Molecular cloning and expression of fatty acid alpha-hydroxylase from Sphingomonas paucimobilis. J Biol Chem 272:23592–23596

    CAS  PubMed  Google Scholar 

  • Maurer S, Urlacher V, Schulze H, Schmid RD (2003) Immobilisation of P450 BM-3 and an NADP + cofactor recycling system: towards a technical application of heme-containing monooxygenases in fine chemical synthesis. Adv Synth Catal 345:802–810

  • Maurer SC, Kuhnel K, Kaysser LA, Eiben S, Schmid RD, Urlacher VB (2005) Catalytic hydroxylation in biphasic systems using CYP102A1 mutants. Adv Synth Catal 347:1090–1098

    CAS  Google Scholar 

  • McIntosh JA, Coelho PS, Farwell CC, Wang ZJ, Lewis JC, Brown TR, Arnold FH (2013) Enantioselective intramolecular C–H amination catalyzed by engineered cytochrome P450 enzymes in vitro and in vivo. Angew Chem Int Ed Engl 52:9309–9312

    CAS  PubMed  Google Scholar 

  • McLean KJ, Girvan HM, Munro AW (2007) Cytochrome P450/redox partner fusion enzymes: biotechnological and toxicological prospects. Expert Opin Drug Metab Toxicol 3:847–863

    CAS  PubMed  Google Scholar 

  • Michizoe J, Ichinose H, Kamiya N, Maruyama T, Goto M (2005) Functionalization of the cytochrome P450cam monooxygenase system in the cell-like aqueous compartments of water-in-oil emulsions. J Biosci Bioeng 99:12–17

    CAS  PubMed  Google Scholar 

  • Mouri T, Michizoe J, Ichinose H, Kamiya N, Goto M (2006) A recombinant Escherichia coli whole cell biocatalyst harboring a cytochrome P450cam monooxygenase system coupled with enzymatic cofactor regeneration. Appl Microbiol Biotechnol 2:514–520

    Google Scholar 

  • Müller CA, Akkapurathu B, Winkler T, Staudt S, Hummel W, Gröger H, Schwaneberg U (2013) In vitro double oxidation of n-heptane with direct cofactor regeneration. Adv Synth Catal 355:1787–1798

  • Munro AW, Girvan HM, McLean KJ (2007) Variations on a (t)heme—novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily. Nat Prod Rep 24:585–609

    CAS  PubMed  Google Scholar 

  • Nelson DR (2009) The cytochrome P450 homepage. Hum Genomics 4:59–65

  • Nelson DR (2013) A world of cytochrome P450s. Philos Trans R Soc Lond B Biol Sci 368:1–4

    Google Scholar 

  • Neunzig I, Widjaja M, Peters FT, Maurer HH, Hehn A, Bourgaud F, Bureik M (2013) Coexpression of CPR from various origins enhances biotransformation activity of human CYPs in S. pombe. Appl Biochem Biotechnol 170:1751–1766

    CAS  PubMed  Google Scholar 

  • Nguyen KT, Virus C, Günnewich N, Hannemann F, Bernhardt R (2012) Changing the regioselectivity of a P450 from C15 to C11 hydroxylation of progesterone. Chembiochem 13:1161–1166

    CAS  PubMed  Google Scholar 

  • Niraula NP, Kanth BK, Sohng JK, Oh TJ (2011) Hydrogen peroxide-mediated dealkylation of 7-ethoxycoumarin by cytochrome P450 (CYP107AJ1) from Streptomyces peucetius ATCC27952. Enzym Microb Technol 48:181–186

    CAS  Google Scholar 

  • Nodate M, Kubota M, Misawa N (2006) Functional expression system for cytochrome P450 genes using the reductase domain of self-sufficient P450RhF from Rhodococcus sp. NCIMB 9784. Appl Microbiol Biotechnol 71:455–462

    CAS  PubMed  Google Scholar 

  • Ogata J, Kanno Y, Itoh Y, Tsugawa H, Suzuki M (2005) Plant biochemistry: anthocyanin biosynthesis in roses. Nature 435:757–758

    CAS  PubMed  Google Scholar 

  • Ogura H, Nishida CR, Hoch UR, Perera R, Dawson JH, Ortiz de Montellano PR (2004) EpoK, a cytochrome P450 involved in biosynthesis of the anticancer agents epothilones A and B. Substrate-mediated rescue of a P450 enzyme. Biochemistry 43:14712–14721

    CAS  PubMed  Google Scholar 

  • O'Keefe DP, Harder PA (1991) Occurrence and biological function of cytochrome P450 monooxygenases in the actinomycetes. Mol Microbiol 5:2099–2105

    PubMed  Google Scholar 

  • O'Keefe DP, Gibson KJ, Emptage MH, Lenstra R, Romesser JA, Litle PJ, Omer CA (1991) Ferredoxins from two sulfonylurea herbicide monooxygenase systems in Streptomyces griseolus. Biochemistry 30:447–455

    PubMed  Google Scholar 

  • Omura T (2013) Contribution of cytochrome P450 to the diversification of eukaryotic organisms. Biotechnol Appl Biochem 60:4–8

    CAS  PubMed  Google Scholar 

  • O’Reilly E, Kohler V, Flitsch SL, Turner NJ (2011) Cytochromes P450 as useful biocatalysts: addressing the limitations. Chem Commun (Camb) 47:2490–2501

    Google Scholar 

  • Otey CR, Bandara G, Lalonde J, Takahashi K, Arnold FH (2006) Preparation of human metabolites of propranolol using laboratory-evolved bacterial cytochromes P450. Biotechnol Bioeng 93:494–499

    CAS  PubMed  Google Scholar 

  • Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Jiang H, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528–532

    CAS  PubMed  Google Scholar 

  • Panicco P, Dodhia VR, Fantuzzi A, Gilardi G (2011) Enzyme-based amperometric platform to determine the polymorphic response in drug metabolism by cytochromes P450. Anal Chem 83:2179–2186

    CAS  PubMed  Google Scholar 

  • Park JW, Lee JK, Kwon TJ, Yi DH, Kim YJ, Moon SH, Suh HH, Kang SM, Park YI (2003) Bioconversion of compactin into pravastatin by Streptomyces sp. Biotechnol Lett 25:1827–1831

    CAS  PubMed  Google Scholar 

  • Peng Y, Yashphe J, Demain AL (1997) Biotransformation of compactin to pravastatin by Actinomadura sp. 2966. J Antibiot (Tokyo) 50:1032–1035

    CAS  Google Scholar 

  • Peterson DH, Murray HC, Eppstein SH, Reineke LM, Weintraub A, Meister PD, Leigh HM (1952) Microbiological transformations of steroids.1. Introduction of oxygen at carbon-11 of progesterone. J Am Chem Soc 74:5933–5936

    CAS  Google Scholar 

  • Peterson JA, Sevrioukova I, Truan G, Graham-Lorence SE (1997) P450BM-3; a tale of two domains—or is it three? Steroids 62:117–123

    CAS  PubMed  Google Scholar 

  • Petzoldt K, Annen K, Laurent H, Wiechert R (1982) Process for the preparation of 11-beta-hydroxy steroids. US Patent, Schering Aktiengesellschaft (Berlin, Germany)

  • Podust LM, Sherman DH (2012) Diversity of P450 enzymes in the biosynthesis of natural products. Nat Prod Rep 29:1251–1266

    CAS  PubMed Central  PubMed  Google Scholar 

  • Prosser DE, Jones G (2004) Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci 29:664–673

    CAS  PubMed  Google Scholar 

  • Reinen J, van Leeuwen JS, Li Y, Sun L, Grootenhuis PD, Decker CJ, Saunders J, Vermeulen NP, Commandeur JN (2011) Efficient screening of cytochrome P450 BM3 mutants for their metabolic activity and diversity toward a wide set of drug-like molecules in chemical space. Drug Metab Dispos 39:1568–1576

    CAS  PubMed  Google Scholar 

  • Rentmeister A, Arnold FH, Fasan R (2009) Chemo-enzymatic fluorination of unactivated organic compounds. Nat Chem Biol 5:26–28

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–943

    CAS  PubMed  Google Scholar 

  • Roberts GA, Grogan G, Greter A, Flitsch SL, Turner NJ (2002) Identification of a new class of cytochrome P450 from a Rhodococcus sp. J Bacteriol 184:3898–3908

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rua F, Sadeghi SJ, Castrignano S, Di Nardo G, Gilardi G (2012) Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs. J Inorg Biochem 117:277–284

    CAS  PubMed  Google Scholar 

  • Ruijssenaars HJ, Sperling EM, Wiegerinck PH, Brands FT, Wery J, de Bont JA (2007) Testosterone 15beta-hydroxylation by solvent tolerant Pseudomonas putida S12. J Biotechnol 131:205–208

    CAS  PubMed  Google Scholar 

  • Rylott EL, Jackson RG, Edwards J, Womack GL, Seth-Smith HM, Rathbone DA, Strand SE, Bruce NC (2006) An explosive-degrading cytochrome P450 activity and its targeted application for the phytoremediation of RDX. Nat Biotechnol 24:216–219

    CAS  PubMed  Google Scholar 

  • Sabbadin F, Hyde R, Robin A, Hilgarth EM, Delenne M, Flitsch S, Turner N, Grogan G, Bruce NC (2010) LICRED: a versatile drop-in vector for rapid generation of redox-self-sufficient cytochrome P450s. Chembiochem 11:987–994

    CAS  PubMed  Google Scholar 

  • Sadeghi SJ, Gilardi G (2013) Chimeric P450 enzymes: activity of artificial redox fusions driven by different reductases for biotechnological applications. Biotechnol Appl Biochem 60:102–110

    CAS  PubMed  Google Scholar 

  • Sadeghi SJ, Meharenna YT, Fantuzzi A, Valetti F, Gilardi G (2000) Engineering artificial redox chains by molecular ‘Lego’. Faraday Discuss:135-153; discussion 171-190

  • Sadeghi SJ, Fantuzzi A, Gilardi G (2011) Breakthrough in P450 bioelectrochemistry and future perspectives. Biochim Biophys Acta 1814:237–248

    CAS  PubMed  Google Scholar 

  • Sadeghi SJ, Ferrero S, Di Nardo G, Gilardi G (2012) Drug-drug interactions and cooperative effects detected in electrochemically driven human cytochrome P450 3A4. Bioelectrochemistry 86:87–91

    CAS  PubMed  Google Scholar 

  • Sakaki T, Sugimoto H, Hayashi K, Yasuda K, Munetsuna E, Kamakura M, Ikushiro S, Shiro Y (2011) Bioconversion of vitamin D to its active form by bacterial or mammalian cytochrome P450. Biochim Biophys Acta 1814:249–256

    CAS  PubMed  Google Scholar 

  • Salazar O, Cirino PC, Arnold FH (2003) Thermostabilization of a cytochrome P450 peroxygenase. Chembiochem 4:891–893

  • Sasaki J, Mikami A, Mizoue K, Omura S (1991) Transformation of 25- and 1 alpha-hydroxyvitamin D3 to 1 alpha, 25-dihydroxyvitamin D3 by using Streptomyces sp. strains. Appl Environ Microbiol 57:2841–2846

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sasaki J, Miyazaki A, Saito M, Adachi T, Mizoue K, Hanada K, Omura S (1992) Transformation of vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 via 25-hydroxyvitamin D3 using Amycolata sp. strains. Appl Microbiol Biotechnol 38:152–157

    CAS  PubMed  Google Scholar 

  • Sawada N, Sakaki T, Yoneda S, Kusudo T, Shinkyo R, Ohta M, Inouye K (2004) Conversion of vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 by Streptomyces griseolus cytochrome P450SU-1. Biochem Biophys Res Commun 320:156–164

    CAS  PubMed  Google Scholar 

  • Sawayama AM, Chen MM, Kulanthaivel P, Kuo MS, Hemmerle H, Arnold FH (2009) A panel of cytochrome P450 BM3 variants to produce drug metabolites and diversify lead compounds. Chemistry (Easton) 15:11723–11729

    CAS  Google Scholar 

  • Scheps D, Honda Malca S, Richter SM, Marisch K, Nestl BM, Hauer B (2011) Synthesis of omega-hydroxy dodecanoic acid based on an engineered CYP153A fusion construct. Microb Biotechnol 6:694–707

    Google Scholar 

  • Schewe H, Kaup BA, Schrader J (2008) Improvement of P450(BM-3) whole-cell biocatalysis by integrating heterologous cofactor regeneration combining glucose facilitator and dehydrogenase in E. coli. Appl Microbiol Biotechnol 78:55–65

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Schiffler B, Bernhardt R (2003) Bacterial (CYP101) and mitochondrial P450 systems-how comparable are they? Biochem Biophys Res Commun 312:223–228

    CAS  PubMed  Google Scholar 

  • Schiffler B, Kiefer M, Wilken A, Hannemann F, Adolph HW, Bernhardt R (2001) The interaction of bovine adrenodoxin with CYP11A1 (cytochrome P450scc) and CYP11B1 (cytochrome P45011beta). Acceleration of reduction and substrate conversion by site-directed mutagenesis of adrenodoxin. J Biol Chem 276:36225–36232

    CAS  PubMed  Google Scholar 

  • Schneider E, Clark DS (2012) Cytochrome P450 (CYP) enzymes and the development of CYP biosensors. Biosens Bioelectron 39:1–13

    PubMed  Google Scholar 

  • Schroer K, Kittelmann M, Lutz S (2010) Recombinant human cytochrome P450 monooxygenases for drug metabolite synthesis. Biotechnol Bioeng 106:699–706

    CAS  PubMed  Google Scholar 

  • Schuckel J, Rylott EL, Grogan G, Bruce NC (2012) A gene-fusion approach to enabling plant cytochromes P450 for biocatalysis. Chembiochem 13:2758–2763

    PubMed  Google Scholar 

  • Serizawa N (2000) Biocatalytic production of pravastatin, an anticholesterol drug. In: Patel RN (ed) Stereoselective biocatalysis, edn. Marcel Dekker, New York-Basel, pp 703–710

    Google Scholar 

  • Serizawa N, Matsuoka T (1991) A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxylation of ML-236B to pravastatin, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Biochim Biophys Acta 1084:35–40

    CAS  PubMed  Google Scholar 

  • Sevrioukova IF, Peterson JA (1995) NADPH-P450 reductase: structural and functional comparisons of the eukaryotic and prokaryotic isoforms. Biochimie 77:562–572

  • Shoji O, Fujishiro T, Nakajima H, Kim M, Nagano S, Shiro Y, Watanabe Y (2007) Hydrogen peroxide dependent monooxygenations by tricking the substrate recognition of cytochrome P450BSbeta. Angew Chem Int Ed Engl 46:3656–3659

    CAS  PubMed  Google Scholar 

  • Shumyantseva VV, Bulko TV, Archakov AI (2005) Electrochemical reduction of cytochrome P450 as an approach to the construction of biosensors and bioreactors. J Inorg Biochem 99:1051–1063

    CAS  PubMed  Google Scholar 

  • Shumyantseva VV, Bulko TV, Kuznetsova GP, Samenkova NF, Archakov AI (2009) Electrochemistry of cytochromes P450: analysis of current-voltage characteristics of electrodes with immobilized cytochromes P450 for the screening of substrates and inhibitors. Biochemistry (Mosc) 74:438–444

  • Sibbesen O, De Voss JJ, Montellano PR (1996) Putidaredoxin reductase-putidaredoxin-cytochrome P450cam triple fusion protein. Construction of a self-sufficient Escherichia coli catalytic system. J Biol Chem 271:22462–22469

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Sono M, Roach MP, Coulter ED, Dawson JH (1996) Heme-containing oxygenases. Chem Rev 96:2841–2888

    CAS  PubMed  Google Scholar 

  • Staudt S, Burda E, Giese C, Müller CA, Marienhagen J, Schwaneberg U, Hummel W, Drauz K, Gröger H (2013) Direct oxidation of cycloalkanes to cycloalkanones with oxygen in water. Angew Chem Int Ed 52:2359–2363

    CAS  Google Scholar 

  • Sugimoto H, Shinkyo R, Hayashi K, Yoneda S, Yamada M, Kamakura M, Ikushiro S, Shiro Y, Sakaki T (2008) Crystal structure of CYP105A1 (P450SU-1) in complex with 1alpha,25-dihydroxyvitamin D3. Biochemistry 47:4017–4027

    CAS  PubMed  Google Scholar 

  • Sundermann A, Oostenbrink C (2013) Molecular dynamics simulations give insight into the conformational change, complex formation, and electron transfer pathway for cytochrome P450 reductase. Protein Sci 22:1183–1195

    PubMed  Google Scholar 

  • Szczebara FM, Chandelier C, Villeret C, Masurel A, Bourot S, Duport C, Blanchard S, Groisillier A, Testet E, Costaglioli P, Cauet G, Degryse E, Balbuena D, Winter J, Achstetter T, Spagnoli R, Pompon D, Dumas B (2003) Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat Biotechnol 21:143–149

    CAS  PubMed  Google Scholar 

  • Teoh KH, Polichuk DR, Reed DW, Covello PS (2009) Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany-Botanique 87:635–642

  • Theurer M, El Baz Y, Koschorreck K, Urlacher VB, Rauhut G, Baro A, Laschat S (2011) Chemoenzymatic synthesis of the C3-C11-fragment of borrelidin. Eur J Org Chem:4241-4249

  • Uhlmann H, Kraft R, Bernhardt R (1994) C-terminal region of adrenodoxin affects its structural integrity and determines differences in its electron transfer function to cytochrome P-450. J Biol Chem 269:22557–22564

    CAS  PubMed  Google Scholar 

  • Urlacher VB (2010) Catalysis with Cytochrome P450 Monooxygenases. In: Anastas PT, Crabtree RH (eds) Handbook of green chemistry, pp 1–25

  • Urlacher VB, Eiben S (2006) Cytochrome P450 monooxygenases: perspectives for synthetic application. Trends Biotechnol 24:324–330

    CAS  PubMed  Google Scholar 

  • van Beilen JB, Funhoff EG, van Loon A, Just A, Kaysser L, Bouza M, Holtackers R, Rothlisberger M, Li Z, Witholt B (2006) Cytochrome P450 alkane hydroxylases of the CYP153 family are common in alkane-degrading eubacteria lacking integral membrane alkane hydroxylases. Appl Environ Microbiol 72:59–65

    PubMed Central  PubMed  Google Scholar 

  • van den Bemd GJ, Chang GT (2002) Vitamin D and vitamin D analogs in cancer treatment. Curr Drug Targets 3:85–94

    PubMed  Google Scholar 

  • Venkateswarlu K, Kelly DE, Kelly SL (1997) Characterization of Saccharomyces cerevisiae CYP51 and a CYP51 fusion protein with NADPH cytochrome P-450 oxidoreductase expressed in Escherichia coli. Antimicrob Agents Chemother 41:776–780

    CAS  PubMed Central  PubMed  Google Scholar 

  • Verma R, Schwaneberg U, Roccatano D (2014) Insight into the redox partner interaction mechanism in cytochrome P450BM-3 using molecular dynamics simulations. Biopolymers 101:197–209

    CAS  PubMed  Google Scholar 

  • Virus C, Bernhardt R (2008) Molecular evolution of a steroid hydroxylating cytochrome P450 using a versatile steroid detection system for screening. Lipids 43:1133–1141

    CAS  PubMed  Google Scholar 

  • von Buhler C, Le-Huu P, Urlacher VB (2013) Cluster screening: an effective approach for probing the substrate space of uncharacterized cytochrome P450s. Chembiochem 14:2189–2198

  • Vottero E, Rea V, Lastdrager J, Honing M, Vermeulen NP, Commandeur JN (2011) Role of residue 87 in substrate selectivity and regioselectivity of drug-metabolizing cytochrome P450 CYP102A1 M11. J Biol Inorg Chem 16:899–912

    CAS  PubMed Central  PubMed  Google Scholar 

  • Watanabe I, Serizawa N (1998) Molecular approaches for production of pravastatin, a HMG-CoA reductase inhibitor: transcriptional regulation of the cytochrome P450sca gene from Streptomyces carbophilus by ML-236B sodium salt and phenobarbital. Gene 210:109–116

  • Watanabe I, Nara F, Serizawa N (1995) Cloning, characterization and expression of the gene encoding cytochrome P-450sca-2 from Streptomyces carbophilus involved in production of pravastatin, a specific HMG-CoA reductase inhibitor. Gene 163:81–85

    CAS  PubMed  Google Scholar 

  • Weber E, Seifert A, Antonovici M, Geinitz C, Pleiss J, Urlacher VB (2010) Screening of a minimal enriched P450 BM3 mutant library for hydroxylation of cyclic and acyclic alkanes. Chem Commun (Camb) 47:944–946

    Google Scholar 

  • Weckbecker A, Hummel W (2006) Cloning, expression, and characterization of an (R)-specific alcohol dehydrogenase from Lactobacillus kefir. Biocatalysis Biotransformation 24:380–389

  • Weis R, Winkler M, Schittmayer M, Kambourakis S, Vink M, Rozzell JD, Glieder A (2009) A diversified library of bacterial and fungal bifunctional cytochrome P450 enzymes for drug metabolite synthesis. Adv Synth Catal 351:2140–2146

    CAS  Google Scholar 

  • Weiss A (2007) Selective microbail oxidations in industry: oxidations of alkanes, fatty acids, heterocyclic compounds, aromatic compounds and glycerol using native or recombinant microorganisms. In: Schmid RD, Urlacher VB (eds) Modern oxidation: enzymes, reactions and applications, edn. Wiley-VCH, Weinheim, pp 193–210

    Google Scholar 

  • Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A, Fickes S, Diola D, Benjamin KR, Keasling JD, Leavell MD, McPhee DJ, Renninger NS, Newman JD, Paddon CJ (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci U S A 109:E111–E118

    CAS  PubMed Central  PubMed  Google Scholar 

  • Whitehouse CJ, Bell SG, Wong LL (2012) P450(BM3) (CYP102A1): connecting the dots. Chem Soc Rev 41:1218–1260

    CAS  PubMed  Google Scholar 

  • WHO (2006) Guidelines for the treatment of malaria. World Health Organization, Geneva

    Google Scholar 

  • WHO (2010) Guidelines for the treatment of malaria. World Health Organization, Geneva

    Google Scholar 

  • Wichmann R, Vasic-Racki D (2005) Cofactor regeneration at the lab scale. Adv Biochem Eng Biotechnol 92:225–260

    CAS  PubMed  Google Scholar 

  • Yang W, Bell SG, Wang H, Zhou W, Hoskins N, Dale A, Bartlam M, Wong LL, Rao Z (2010) Molecular characterization of a class I P450 electron transfer system from Novosphingobium aromaticivorans DSM12444. J Biol Chem 285:27372–27384

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zehentgruber D, Hannemann F, Bleif S, Bernhardt R, Lutz S (2010) Towards preparative scale steroid hydroxylation with cytochrome P450 monooxygenase CYP106A2. Chembiochem 11:713–721

    CAS  PubMed  Google Scholar 

  • Zollner A, Nogues I, Heinz A, Medina M, Gomez-Moreno C, Bernhardt R (2004) Analysis of the interaction of a hybrid system consisting of bovine adrenodoxin reductase and flavodoxin from the cyanobacterium Anabaena PCC 7119. Bioelectrochemistry 63:61–65

    CAS  PubMed  Google Scholar 

  • Zollner A, Buchheit D, Meyer MR, Maurer HH, Peters FT, Bureik M (2010) Production of human phase 1 and 2 metabolites by whole-cell biotransformation with recombinant microbes. Bioanalysis 2:1277–1290

    PubMed  Google Scholar 

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Acknowledgments

The work was generously supported by the BMBF grant FKZ 031A166. The authors thank Antje Eiden-Plach for technical support.

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Bernhardt, R., Urlacher, V.B. Cytochromes P450 as promising catalysts for biotechnological application: chances and limitations. Appl Microbiol Biotechnol 98, 6185–6203 (2014). https://doi.org/10.1007/s00253-014-5767-7

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