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Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part I: processes with isolated enzymes

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Abstract

Enzymes are able to perform reactions under mild conditions, e.g., pH and temperature, with remarkable chemo-, regio-, and stereoselectivity. Because of this feature, the number of biocatalysts used in organic synthesis has rapidly increased during the last decades, especially for the production of chiral compounds. The present review highlights biotechnological processes for the production of chiral alcohols by reducing prochiral ketones. These reactions can be catalyzed by either isolated enzymes or whole cells that exhibit ketone-reducing activity. The use of isolated enzymes is often preferred because of a higher volumetric productivity and the absence of side reactions. Both types of catalysts have also deficiencies limiting their use in synthesis of chiral alcohols. Because reductase-catalyzed reactions are dependent on cofactors, one major task in process development is to provide an effective method for regeneration of the consumed cofactors. In this paper, strategies for cofactor regeneration in biocatalytic ketone reduction are reviewed. Furthermore, different processes carried out on laboratory and industrial scales using isolated enzymes are presented. Attention is turned to process parameters, e.g., conversion, yield, enantiomeric excess, and process strategies, e.g., the application of biphasic systems or methods of in situ (co)product recovery. The biocatalytic production of chiral alcohols utilizing whole cells is presented in part II of this review (Goldberg et al., Appl Microbiol Biotechnol, 2007).

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References

  • Abril O, Whitesides GM (1982) Hybrid organometallic/enzymatic catalyst systems: regeneration of NADH using dihydrogen. J Am Chem Soc 104:1552–1554

    CAS  Google Scholar 

  • Adam W, Lazarus M, Saha-Möller CR, Schreier P (1999) Biocatalytic synthesis of optically active α-oxyfunctionalized carbonyl compounds. Acc Chem Res 32:837–845

    CAS  Google Scholar 

  • Avi M, Fechter MH, Gruber K, Belaj F, Pöchlauer P, Griengl H (2004) Hydroxynitrile lyase catalyzed synthesis of heterocyclic (R)- and (S)-cyanohydrins. Tetrahedron 60:10411–10418

    CAS  Google Scholar 

  • Bhaduri S, Mathur P, Payra P, Sharma K (1998) Coupling of catalyses by carbonyl clusters and dehydrogenases: reduction of pyruvate to l-lactate by dihydrogen. J Am Chem Soc 120:12127–12128

    CAS  Google Scholar 

  • Biade AE, Bourdillon C, Lava JM, Mairesse G, Moiroux J (1992) Complete conversion of l-lactate into d-lactate. A generic approach involving enzymatic catalysis, electrochemical oxidation of NADH, and electrochemical reduction of pyruvate. J Am Chem Soc 114:893–897

    CAS  Google Scholar 

  • Blaser HU, Malan C, Pugin B, Spindler F, Steiner H, Studer M (2003) Selective hydrogenation for fine chemicals: recent trends and new developments. Adv Synth Catal 345:103–151

    CAS  Google Scholar 

  • Bommarius AS, Schwarm M, Stingl K, Kottenhahn M, Huthmacher K, Drauz K (1995) Synthesis and use of enantiomerically pure tert-leucine. Tetrahedron Asymmetry 6:2851–2888

    CAS  Google Scholar 

  • Bornscheuer U, Reif OW, Lausch R, Freitag R, Scheper T, Kolisis FN, Menge U (1994) Lipase of Pseudomonas cepacia for biotechnological purposes: purification, crystallization and characterization. Biochim Biophys Acta 1201:55–60

    CAS  PubMed  Google Scholar 

  • Bortolini OMS (1997) An easy approach to the synthesis of optically active vic-diols: a new single-enzyme system. J Org Chem 62:1854–1856

    CAS  Google Scholar 

  • Breuer M, Ditrich K, Habicher T, Hauer B, Keßeler M, Stürmer R, Zelinski T (2004) Industrielle Verfahren zur Herstellung von optisch aktiven Zwischenprodukten. Angew Chem 116:806–843 (also in Angew Chem Int Ed 43:788–824)

    Google Scholar 

  • Buchholz S, Gröger H (2006) Enantioselective biocatalytic reduction of ketones for the synthesis of optically active alcohols. In: Patel RN (ed) Biocatalysis in the pharmaceutical and biotechnology industries. Taylor & Francis, New York, pp 757–790

    Google Scholar 

  • Buque-Taboada EM, Straathof AJJ, Heijnen JJ, van der Wielen LAM (2006) In situ product recovery (ISPR) by crystallization: basic principles, design, and potential applications in whole-cell biocatalysis. Appl Microbiol Biotechnol 71:1–12

    CAS  PubMed  Google Scholar 

  • Choudary BM, Chowdari NS, Madhi S, Kantam ML (2001) A trifunctional catalyst for the synthesis of chiral diols. Angew Chem 113:4755–4759 (also in Angew Chem Int Ed 40:4655–4759)

    Google Scholar 

  • Costas AMG, White AK, Metcalf WW (2001) Purification and characterization of a novel phosphorus-oxidizing enzyme from Pseudomonas stutzeri WM88. J Biol Chem 276:17429–17436

    CAS  PubMed  Google Scholar 

  • Daußmann T, Hennemann HG, Rosen TC (2006a) Enzymatische technologien zur synthese chiraler alkohol-derivate. Chem Ing Tech 78:249–255

    Google Scholar 

  • Daußmann T, Dünkelmann P, Lütz S (2006b) Chiral alcohols. CHEManager (Europe) 3:8

    Google Scholar 

  • Daußmann T, Rosen TC, Dünkelmann P (2006c) Oxidoreductases and hydroxynitrilase lyases: complementary enzymatic technologies for chiral alcohols. Eng Life Sci 6:125–129

    Google Scholar 

  • Davis C, Grate J, Gray D, Gruber J, Huismann G, Ma S, Newman L, Sheldon R (2005) Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives. Codexis, Patent no. WO04015132

  • Degenring D, Schröder I, Wandrey C, Liese A, Greiner L (2004) Resolution of 1,2-diols by enzyme-catalyzed oxidation with anodic, mediated cofactor regeneration in the extractive membrane reactor: gaining insight by adaptive simulation. Org Process Res Dev 8:213–218

    CAS  Google Scholar 

  • Demir AS, Şeşenoglu Ö, Eren E, Hosrik B, Pohl M, Janzen E, Kolter D, Feldmann R, Dünkelmann P, Müller M (2002) Enantioselective synthesis of α-hydroxy ketones via benzaldehyde lyase-catalyzed C–C bond formation reaction. Adv Synth Catal 344:96–103

    CAS  Google Scholar 

  • Detry J, Rosenbaum T, Lütz S, Hahn D, Jaeger KE, Müller M, Eggert T (2006) Biocatalytic production of enantiopure cyclohexane-trans-1,2-diol using extracellular lipases from Bacillus subtilis. Appl Microbiol Biotechnol 72:1107–1116

    CAS  PubMed  Google Scholar 

  • Domínguez de María P, Stillger T, Pohl M, Wallert S, Drauz K, Groger H, Trauthwein H, Liese A (2006) Preparative enantioselective synthesis of benzoins and (R)-2-hydroxy-1-phenylpropanone using benzaldehyde lyase. J Mol Catal B Enzym 38:43–47

    Google Scholar 

  • Eckstein M, Villela M, Liese A, Kragl U (2004) Use of an ionic liquid in a two-phase system to improve an alcohol dehydrogenase catalysed reduction. Chem Commun 9:1084–1085

    Google Scholar 

  • Elend C, Schmeisser C, Leggewie C, Babiak P, Carballeira JD, Steele HL, Reymond JL, Jaeger KE, Streit WR (2006) Isolation and biochemical characterization of two novel metagenome-derived esterases. Appl Environ Microbiol 72:3637–3645

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ernst M, Kaup B, Müller M, Bringer-Meyer S, Sahm H (2005) Enantioselective reduction of carbonyl compounds by whole-cell biotransformation, combining a formate dehydrogenase and a (R)-specific alcohol dehydrogenase. Appl Microbiol Biotechnol 66:629–634

    CAS  PubMed  Google Scholar 

  • Faber K (2004) Biotransformations in organic chemistry (5th edn.). Springer, Berlin

    Google Scholar 

  • Fechter MH, Griengl H (2004) Hydroxynitrile lyases: biological sources and application as biocatalysts. Food Technol Biotechnol 42:287–294

    CAS  Google Scholar 

  • Ferloni C, Heinemann M, Hummel W, Daußmann T, Büchs J (2004) Optimization of enzymatic gas-phase reactions by increasing the long-term stability of the catalyst. Biotechnol Prog 20:975–978

    CAS  PubMed  Google Scholar 

  • Findrik Z, Vasic-Racki D, Lütz S, Daußmann T, Wandrey C (2005) Kinetic modelling of acetophenone reduction catalyzed by alcohol dehydrogenase from Thermoanaerobacter sp. Biotechnol Lett 27:1087–1095

    CAS  PubMed  Google Scholar 

  • Gaisberger RP, Fechter MH, Griengl H (2004) The first hydroxynitrile lyase catalysed cyanohydrin formation in ionic liquids. Tetrahedron Asymmetry 15:2959–2963

    CAS  Google Scholar 

  • Goldberg K, Edegger K, Kroutil W, Liese A (2006) Overcoming the thermodynamic limitation in asymmetric hydrogen transfer reactions catalyzed by whole cells. Biotechnol Bioeng 95:192–198

    CAS  PubMed  Google Scholar 

  • Goldberg K, Schroer K, Lütz S, Liese A (2007) Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part II: whole cell reductions. Appl Microbiol Biotechnol (in this issue)

  • Greiner L, Müller DH, van den Ban ECD, Wöltinger J, Wandrey C, Liese A (2003) Membrane aerated hydrogenation: enzymatic and chemical homogeneous catalysis. Adv Synth Catal 345:679–683

    CAS  Google Scholar 

  • Griengl H, Hickel A, Johnson DV, Kratky C, Schmidt M, Schwab H (1997) Enzymatic cleavage and formation of cyanohydrins: a reaction of biological and synthetic relevance. Chem Commun 1933–1940

  • Haberland J, Hummel W, Daußmann T, Liese A (2002) New continuous production process for enantiopure (2R,5R)-hexanediol. Org Process Res Dev 6:458–462

    CAS  Google Scholar 

  • Hildebrand F, Lütz S (2006) Immobilisation of alcohol dehydrogenase from Lactobacillus brevis and its application in a plug-flow reactor. Tetrahedron Asymmetry 17:3219–3225

    CAS  Google Scholar 

  • Hildebrand F, Kühl S, Pohl M, Vasic-Racki D, Müller M, Wandrey C, Lütz S (2006) The production of (R)-2-hydroxy-1-phenyl-propan-1-one derivatives by benzaldehyde lyase from Pseudomonas fluorescens in a continuously operated membrane reactor. Biotechnol Bioeng 96(5):835–843

    Google Scholar 

  • Hilt G, Jarbawi T, Heineman WR, Steckhan E (1997) An analytical study of the redox behavior of 1,10-phenanthroline-5,6-dione, its transition-metal complexes, and its N-monomethylated derivative with regard to their efficiency as mediators of NAD(P)+ regeneration. Chem Eur 3:79–88

    CAS  Google Scholar 

  • Hollmann F, Schmid A (2004) Electrochemical regeneration of oxidoreductases for cell-free biocatalytic redox reactions. Biocatal Biotransform 22:63–88

    CAS  Google Scholar 

  • Hollmann F, Kleeb A, Otto K, Schmid A (2006) Corrigendum to “Coupled chemoenzymatic transfer hydrogenation catalysis for enantioselective reduction and oxidation reactions”. Tetrahedron Asymmetry 17:867–868

    CAS  Google Scholar 

  • Honda K, Ishige T, Kataoka M, Shimizu S (2006) Microbial and enzymatic processes for the production of chiral compounds. In: Patel RN (ed) Biocatalysis in the pharmaceutical and biotechnology industries. Taylor & Francis, New York, pp 529–546

    Google Scholar 

  • Hummel W (1997) New alcohol dehydrogenases for the synthesis of chiral compounds. Adv Biochem Eng Biotechnol 58:145–184

    CAS  PubMed  Google Scholar 

  • Hummel W, Kula MR (1989) Dehydrogenases for the synthesis of chiral compounds. Eur J Biochem 184:1–13

    CAS  PubMed  Google Scholar 

  • Hummel W, Abokitse K, Drauz K, Rollmann C, Gröger H (2003) Towards a large-scale asymmetric reduction process with isolated enzymes: expression of an (S)-alcohol dehydrogenase in E. coli and studies on the synthetic potential of this biocatalyst. Adv Synth Catal 345:153–159

    CAS  Google Scholar 

  • Jaeger KE, Eggert T (2002) Lipases for biotechnology. Curr Opin Biotechnol 13:390–397

    CAS  PubMed  Google Scholar 

  • Jaeger KE, Schneidinger B, Rosenau F, Werner M, Lang D, Dijkstra BW, Schimossek K, Zonta A, Reetz MT (1997) Bacterial lipases for biotechnological applications. J Mol Catal B Enzym 3:3–12

    CAS  Google Scholar 

  • Johannes TW, Woodyer RD, Zhao H (2007) Efficient regeneration of NADPH using an engineered phosphite dehydrogenase. Biotechnol Bioeng 96:18–26

    CAS  PubMed  Google Scholar 

  • Jones JB, Sneddon DW, Higgins W, Lewis A (1972) Preparative-scale reductions of cyclic ketone and aldehyde substrates of horse liver alcohol dehydrogenase with in situ sodium dithionite recycling of catalytic amounts of NAD. J Chem Soc Chem Commun 1972:856–857

    Google Scholar 

  • Julliard M, Le Petit J, Ritz P (2004) Regeneration of NAD+ cofactor by photosensitized electron transfer in an immobilized alcohol dehydrogenase system. Biotechnol Bioeng 28:1774–1779

    Google Scholar 

  • Kataoka M, Rohani LPS, Wada M, Kita K, Yanase H, Urabe I, Shimizu S (1998) Escherichia coli transformant expressing the glucose dehydrogenase gene from Bacillus megaterium as a cofactor regenerator in a chiral alcohol production system. Biosci Biotechnol Biochem 62:167–169

    CAS  PubMed  Google Scholar 

  • Kihumbu D, Stillger T, Hummel W, Liese A (2002) Enzymatic synthesis of all stereoisomers of 1-phenylpropane-1,2-diol. Tetrahedron Asymmetry 13:1069–1072

    CAS  Google Scholar 

  • Kim MJ, Whitesides GM (1988) l-Lactate dehydrogenase: substrate specificity and use as a catalyst in the synthesis of homochiral 2-hydroxy acids. J Am Chem Soc 110:2959–2964

    CAS  Google Scholar 

  • Kizaki N, Yasohara Y, Hasegawa J, Wada M, Kataoka M, Shimizu S (2001) Synthesis of optically pure ethyl (S)-4-chloro-3-hydroxybutanoate by Escherichia coli transformant cells coexpressing the carbonyl reductase and glucose dehydrogenase genes. Appl Microbiol Biotechnol 55:590–595

    CAS  PubMed  Google Scholar 

  • Klibanov AM, Puglisi AV (1980) The regeneration of coenzymes using immobilized hydrogenase. Biotechnol Lett 2:445–450

    CAS  Google Scholar 

  • Koike T, Murata K, Ikariya T (2000) Stereoselective synthesis of optically active α-hydroxy ketones and anti-1,2-diols via asymmetric transfer hydrogenation of unsymmetrically substituted 1,2-diketones. Org Lett 2:3833–3836

    CAS  PubMed  Google Scholar 

  • Kosjek B, Stampfer W, Pogorevc M, Goessler W, Faber K, Kroutil W (2004) Purification and characterization of a chemotolerant alcohol dehydrogenase applicable to coupled redox reactions. Biotechnol Bioeng 86:55–62

    CAS  PubMed  Google Scholar 

  • Kragl U, Eckstein M, Kaftzik N (2002) Enzyme catalysis in ionic liquids. Curr Opin Biotechnol 13:565–571

    CAS  PubMed  Google Scholar 

  • Kruse W, Hummel W, Kragl U (1996) Alcohol-dehydrogenase-catalyzed production of chiral hydrophobic alcohols. A new approach leading to a nearly waste-free process. Recl Trav Chim Pays-Bas 115:239–243

    CAS  Google Scholar 

  • Kula MR, Kragl U (2000) In: Patel RN (ed) Stereoselective biocatalysis. Marcel Dekker, New York

    Google Scholar 

  • Kurlemann N, Liese A (2004) Immobilization of benzaldehyde lyase and its application as a heterogeneous catalyst in the continuous synthesis of a chiral 2-hydroxy ketone. Tetrahedron Asymmetry 15:2955–2958

    CAS  Google Scholar 

  • Lamare S, Legoy MD, Graber M (2004) Solid/gas bioreactors: powerful tools for fundamental research and efficient technology for industrial applications. Green Chem 6:445–458

    CAS  Google Scholar 

  • Leksawasdi N, Chow YYS, Breuer M, Hauer B, Rosche B, Rogers PL (2004) Kinetic analysis and modelling of enzymatic (R)-phenylacetylcarbinol batch biotransformation process. J Biotechnol 111:179–189

    CAS  PubMed  Google Scholar 

  • Leonida MD (2001) Redox enzymes used in chiral syntheses coupled to coenzyme regeneration. Curr Med Chem 8:345–369

    CAS  PubMed  Google Scholar 

  • Liese A, Karutz M, Kamphuis J, Wandrey C, Kragl U (1996) Enzymatic resolution of 1-phenyl-1,2-ethanediol by enantioselective oxidation: overcoming product inhibition by continuous extraction. Biotechnol Bioeng 51:544–550

    CAS  PubMed  Google Scholar 

  • Liese A, Zelinski T, Kula MR, Kierkels H, Karutz M, Kragl U, Wandrey C (1998) A novel reactor concept for the enzymatic reduction of poorly soluble ketones. J Mol Catal B Enzym 4:91–99

    CAS  Google Scholar 

  • Liese A, Seelbach C, Wandrey C (2006) Industrial biotransformations (2nd edn.). GmbH, Weinheim

    Google Scholar 

  • Liu J, Hsu CC, Wong CH (2004) Sequential aldol condensation catalyzed by DERA mutant Ser238Asp and a formal total synthesis of atorvastatin. Tetrahedron Lett 45:2439–2441

    CAS  Google Scholar 

  • Lütz S (2006) Transition metal catalyzed regeneration of nicotineamide cofactors. In: de Vries JG, Elsevier CJ (eds) The handbook of homogeneous hydrogenation (vol III). GmbH, Weinheim, pp 1471–1482

    Google Scholar 

  • Lye GJ, Woodley JM (1999) Application of in situ product-removal techniques to biocatalytic processes. Trends Biotechnol 17:395–402

    CAS  PubMed  Google Scholar 

  • Makino Y, Ding JY, Negoro S, Urabe I, Okada H (1989) Purification and characterization of a new glucose dehydrogenase from vegetative cells of Bacillus megaterium. J Ferment Bioeng 67:374–379

    CAS  Google Scholar 

  • McWhirter RB, Klapper MH (1990) Semiquinone radicals of methylamine dehydrogenase, methoxatin, and related o-quinones: a pulse radiolysis study. Biochemistry 29:6919–6926

    CAS  PubMed  Google Scholar 

  • Mertens R, Liese A (2004) Biotechnological application of hydrogenases. Curr Opin Biotechnol 15:343–348

    CAS  PubMed  Google Scholar 

  • Mertens R, Greiner L, van den Ban ECD, Haaker HBCM, Liese A (2003) Practical applications of hydrogenase I from Pyrococcus furiosus for NADPH generation and regeneration. J Mol Catal B Enzym 24–25:39–52

    Google Scholar 

  • Mochizuki N, Hiramatsu S, Sugai T, Ohta H, Morita H, Itokawa H (1995) Improved conditions for the production and characterization of 1-arylpropane-1,2-diols and related compounds. Biosci Biotechnol Biochem 59:2282–2291

    CAS  Google Scholar 

  • Müller M (2005) Chemoenzymatische synthese von bausteinen für Statin-Seitenketten. Angew Chem 117:366–369 (also in Angew Chem Int Ed 44:362–365)

    Google Scholar 

  • Neuhauser W, Steininger M, Haltrich D, Kulbe KD, Nidetzky B (1998) A pH-controlled fed-batch process can overcome inhibition by formate in NADH-dependent enzymatic reductions using formate dehydrogenase-catalyzed coenzyme regeneration. Biotechnol Bioeng 60:278–282

    Google Scholar 

  • Nidetzky B, Neuhauser W, Haltrich D, Kulbe KD (1996) Continuous enzymatic production of xylitol with simultaneous coenzyme regeneration in a charged membrane reactor. Biotechnol Bioeng 52:387–396

    CAS  PubMed  Google Scholar 

  • Orlich B, Berger H, Lade M, Schomacker R (2000) Stability and activity of alcohol dehydrogenases in W/O-emulsions: enantioselective reduction including cofactor regeneration. Biotechnol Bioeng 70:638–646

    CAS  PubMed  Google Scholar 

  • Patel RN, Banerjee A, McNamee CG, Brzozowski D, Hanson RL, Szarka LJ (1993) Enantioselective Microbial reduction of 3,5-dioxo-6-(benzyloxy) hexanoic acid, ethyl-ester. Enzyme Microb Technol 15:1014–1021

    CAS  Google Scholar 

  • Peters J (1998) Dehydrogenases – characteristics, design of reaction conditions, and applications. In: Rehm HJ, Reed G (eds) Biotechnology Vol 8a: Biotransformations I, 2nd edn. Wiley-VCH Verlag GmbH, Weinheim, pp 393–460

    Google Scholar 

  • Pohl M, Liese A (2006) Industrial processes using lyases for C–C, C–N and C–O bond formation. In: Patel RN (ed) Biocatalysis in the pharmaceutical and biotechnology industries. Taylor & Francis, New York, pp 661–676

    Google Scholar 

  • Raunio R, Lilius EM (1971) Effect of dithionite on enzyme activities in vivo. Enzymologia 40:360–368

    CAS  PubMed  Google Scholar 

  • Reetz MT, Zonta A, Schimossek K, Liebeton K, Jaeger KE (1997) Erzeugung enantioselektiver biokatalysatoren für die organische chemie durch in-vitro-evolution. Angew Chem 109:2961–2963 (also in Angew Chem Int Ed Engl 36:2830–2832)

    Google Scholar 

  • Rickus JL, Tobin AJ, Zink JI, Dunn B (2002) Photochemical enzyme co-factor regeneration: towards continuous glutamate monitoring with a sol–gel optical biosensor. Mater Res Soc Symp Proc 723:155–160

    CAS  Google Scholar 

  • Rissom S, Beliczey J, Giffels G, Kragl U, Wandrey C (1999) Asymmetric reduction of acetophenone in membrane reactors: comparison of oxazaborolodine and alcohol dehydrogenase catalyzed processes. Tetrahedron Asymmetry 10:923–928

    CAS  Google Scholar 

  • Rosche B, Sandford V, Breuer M, Hauer B, Rogers PL (2002) Enhanced production of R-phenylacetylcarbinol (R-PAC) through enzymatic biotransformation. J Mol Catal B Enzym 19–20:109–115

    Google Scholar 

  • Rosen TC, Daußmann T, Stohrer J (2004) Bioreduction forms optically active 3-hydroxyesters. Speciality Chemicals Magazine, April, pp 39–40

  • Schmid A, Dordick JS, Hauer B, Kiener A, Wubbolts M, Witholt B (2001) Industrial biocatalysis today and tomorrow. Nature 409:258–268

    CAS  PubMed  Google Scholar 

  • Schmidt E, Ghisalba O, Gygax D, Sedelmeier G (1992) Optimization of a process for the production of (R)-2-hydroxy-4-phenylbutyric acid—an intermediate for inhibitors of angiotensin converting enzyme. J Biotechnol 24:315–327

    CAS  PubMed  Google Scholar 

  • Schröder I, Steckhan E, Liese A (2003) In situ NAD+ regeneration using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) as an electron transfer mediator. J Electroanal Chem 541:109–115

    Google Scholar 

  • Schubert T, Hummel W, Müller M (2002) Highly enantioselective preparation of multifunctionalized propargylic building blocks. Angew Chem 114:656–659 (also in Angew Chem Int Ed 41:634–637)

    Google Scholar 

  • Seelbach K, Riebel B, Hummel W, Kula MR, Tishkov VI, Egorov AM, Wandrey C, Kragl U (1996) A novel, efficient regenerating method of NADPH using a new formate dehydrogenase. Tetrahedron Lett 31:1377–1380

    Google Scholar 

  • Simon H, Bader J, Gunther H, Neumann S, Thanos J (1985) Chirale verbindungen durch biokatalytische reduktionen. Angew Chem 97:541–555 (also in Angew Chem Int Ed Engl 24:539–553)

    CAS  Google Scholar 

  • St. Clair N, Wang YF, Margolin AL (2000) Cofactor-bound cross-linked enzyme crystals (CLEC) of alcohol dehydrogenase. Angew Chem 112:388–391 (also in Angew Chem Int Ed 39:380–383)

    Google Scholar 

  • Stark D, von Stockar U (2003) In situ product removal (ISPR) in whole cell biotechnology during the last twenty years. In: Scheper T (ed) Advances in biochemical engineering/biotechnology (vol 80). Springer, Berlin Heidelberg New York, pp 149–175

    Google Scholar 

  • Steckhan E, Herrmann S, Ruppert R, Thömmes J, Wandrey C (1990) Kontinuierliche Erzeugung von NADH aus NAD+ und Formiat mit einem molekulargewichtsvergrößerten Homogenkatalysator in einem Membranreaktor. Angew Chem 102:445–447 (also in Angew Chem Int Ed Engl 29:388–390)

    CAS  Google Scholar 

  • Steckhan E, Herrmann S, Ruppert R, Dietz E, Frede M, Spika E (1991) Analytical study of a series of substituted (2,2′-bipyridyl) (pentamethylcyclopentadienyl)rhodium and -iridium complexes with regard to their effectiveness as redox catalysts for the indirect electrochemical and chemical reduction of NAD(P)+. Organometallics 10:1568–1577

    CAS  Google Scholar 

  • Stillger T, Bönitz M, Filho MV, Liese A (2002) Überwindung von thermodynamischen Limitierungen in substratgekoppelten Cofaktorregenerierungsverfahren. Chem Ing Tech 74:1035–1039

    CAS  Google Scholar 

  • Stillger T, Pohl M, Wandrey C, Liese A (2006) Reaction engineering of benzaldehyde lyase from Pseudomonas fluorescens catalyzing enantioselective C–C bond formation. Org Process Res Dev 10:1172–1177

    CAS  Google Scholar 

  • Takors R (2004) Ganzzell-ISPR-Prozessentwicklung: chancen und risiken. Chem Ing Tech 76:1857–1864

    CAS  Google Scholar 

  • Tao JH, McGee K (2002) Development of a continuous enzymatic process for the preparation of (R)-3-(4-fluorophenyl)-2-hydroxy propionic acid. Org Process Res Dev 6:520–524

    CAS  Google Scholar 

  • Tishkov VI, Galkin AG, Fedorchuk VV, Savitsky PA, Rojkova AM, Gieren H, Kula MR (1999) Pilot scale production and isolation of recombinant NAD+- and NADP+-specific formate dehydrogenases. Biotechnol Bioeng 64:187–193

    CAS  PubMed  Google Scholar 

  • Trivedi A, Heinemann M, Spieß AC, Daußmann T, Büchs J (2005) Optimization of adsoptive immobilization of alcohol dehydrogenase. J Biosci Bioeng 99:340–347

    CAS  PubMed  Google Scholar 

  • Trivedi A, Spieß AC, Daußmann T, Büchs J (2006) Study on mesophilic and thermophilic alcohol dehydrogenases in gas-phase reaction. Biotechnol Prog 22:454–458

    CAS  PubMed  Google Scholar 

  • van Beilen JB, Duetz WA, Schmid A, Witholt B (2003) Practical issues in the application of oxygenases. Trends Biotechnol 21:170–177

    PubMed  Google Scholar 

  • Van Rantwijk F, Lau RM, Sheldon RA (2003) Biocatalytic transformations in ionic liquids. Trends Biotechnol 21:131–138

    PubMed  Google Scholar 

  • Villela M, Stillger T, Müller M, Liese A, Wandrey C (2003) Is logP a convenient criterion to guide the choice of solvents for biphasic enzymatic reactions? Angew Chem 115:3101–3104 (also in Angew Chem Int Ed 42:2993–2996)

    Google Scholar 

  • von Scala C, Fässler P, Gerla J, Maus E (2005) Kontinuierliche herstellung von kosmetischen fettsäureestern mittels reaktivdestillation und pervaporation. Chem Ing Tech 77:1809–1813

    Google Scholar 

  • Vrtis JM, White AK, Metcalf WW, van der Donk WA (2002) Phosphite dehydrogenase: a versatile cofactor-regeneration enzyme. Angew Chem 114:3391–3393 (also in Angew Chem Int Ed 41:3257–3259)

    Google Scholar 

  • Vuorilehto K, Lütz S, Wandrey C (2004) Indirect electrochemical reduction of nicotinamide coenzymes. Bioelectrochemistry 65:1–7

    CAS  PubMed  Google Scholar 

  • Wagenknecht PS, Penney JM, Hembre RT (2003) Transition-metal-catalyzed regeneration of nicotinamide coenzymes with hydrogen. Organometallics 22:1180–1182

    CAS  Google Scholar 

  • Wallner SR, Bauer M, Würdemann C, Wecker P, Glöckner FO, Faber K (2005) Highly enantioselective sec-alkyl sulfatase activity of the marine planctomycete Rhodopirellula baltica shows retention of configuration. Angew Chem 117:6539–6542 (also in Angew Chem Int Ed 44:6381–6384)

    Google Scholar 

  • Walsh C (1980) Flavin coenzymes: at the crossroads of biological redox chemistry. Acc Chem Res 13:148–155

    CAS  Google Scholar 

  • Wandrey C (2004) Biochemical reaction engineering for redox reactions. Chem Rec 4:254–265

    CAS  PubMed  Google Scholar 

  • Weckbecker A, Hummel W (2004) Improved synthesis of chiral alcohols with Escherichia coli cells co-expressing pyridine nucleotide transhydrogenase, NADP+-dependent alcohol dehydrogenase and NAD+-dependent formate dehydrogenase. Biotechnol Lett 26:1739–1744

    CAS  PubMed  Google Scholar 

  • Weckbecker A, Hummel W (2005) Glucose dehydrogenase for the regeneration of NADPH and NADH. In: Barredo JL (ed) Microbial enzymes and biotransformations. Humana, Totowa, NJ, pp 225–238

    Google Scholar 

  • Weuster-Botz D, Paschold H, Striegel B, Gieren H, Kula MR, Wandrey C (1994) Continuous computer controlled production of formate dehydrogenase (FDH) and isolation on a pilot scale. Chem Eng Technol 17:131–137

    CAS  Google Scholar 

  • Wichmann R, Vasic-Racki D (2005) Cofactor regeneration at the lab scale. In: Kragl U (ed) Advances in biochemical engineering/biotechnology (vol 92). Springer, Berlin Heidelberg New York, pp 225–260

    Google Scholar 

  • Willner I, Maidan R, Shapira M (1990) Thermal and photochemical regeneration of nicotinamide cofactors and a nicotinamide model Compound Using a water-soluble rhodium phosphine catalyst. J Chem Soc Perkin Trans 2:559–564

    Google Scholar 

  • Wolberg M, Hummel W, Wandrey C, Müller M (2000) Highly regio- and enantioselective reduction of 3,5-dioxocarboxylates. Angew Chem 112:4476–4478 (also in Angew Chem Int Ed 39:4306–4308)

    Google Scholar 

  • Wong CH, Daniels L, Orme-Johnson WH, Whitesides GM (1981) Enzyme-catalyzed organic synthesis: NAD(P)H regeneration using dihydrogen and the hydrogenase from Methanobacterium thermoautotrophicum. J Am Chem Soc 103:6227–6238

    CAS  Google Scholar 

  • Yuan R, Watanabe S, Kuwabata S, Yoneyama H (1997) Asymmetric electroreduction of ketone and aldehyde derivatives to the corresponding alcohols using alcohol dehydrogenase as an electrocatalyst. J Org Chem 62:2494–2499

    CAS  PubMed  Google Scholar 

  • Zelinski T, Liese A, Wandrey C, Kula MR (1999) Asymmetric reductions in aqueous media: enzymatic synthesis in cyclodextrin containing buffers. Tetrahedron Asymmetry 10:1681–1687

    CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Technical Biocatalysis, Hamburg University of Technology, 21073, Hamburg, Germany

    Katja Goldberg & Andreas Liese

  2. Institute of Biotechnology 2, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany

    Kirsten Schroer & Stephan Lütz

Authors
  1. Katja Goldberg
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  2. Kirsten Schroer
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  3. Stephan Lütz
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  4. Andreas Liese
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Corresponding author

Correspondence to Andreas Liese.

Additional information

Katja Goldberg and Kirsten Schroer did equally contribute to this review.

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Goldberg, K., Schroer, K., Lütz, S. et al. Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part I: processes with isolated enzymes. Appl Microbiol Biotechnol 76, 237–248 (2007). https://doi.org/10.1007/s00253-007-1002-0

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  • DOI: https://doi.org/10.1007/s00253-007-1002-0

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