2.1.1 Cyanohydrin Formation/Henry Reaction

Abstract

Enantiopure cyanohydrins and β-nitro alcohols serve as versatile building blocks for a broad range of chemical and enzymatic reactions, resulting in highly valuable products for many applications. Hydroxynitrile lyases comprise a diverse group of enzymes that catalyze the reversible cleavage of cyanohydrins to carbonyl compounds and hydrogen cyanide. The enzymes have been studied broadly concerning their substrate scope, specificity, structure, and reaction mechanism, and many have been successfully applied and engineered for the synthesis of cyanohydrins from laboratory to industrial scale. Both R- and S-cyanohydrins are accessible from a broad variety of substrates and, in most cases, high yields and enantiopurities can be obtained after enzyme and reaction engineering. Recent progress in the development and optimization of heterologous expression systems make recombinant hydroxynitrile lyases available in the quantities needed for industrial production. The procedures for safe handling of cyanides are also well-defined and established. In addition, some hydroxynitrile lyases are able to catalyze the nonnatural asymmetric Henry reaction. Although the enzyme activities are rather low, the enzymatic synthesis of enantiopure β-nitro alcohols shows promising results.

Key words

hydroxynitrile lyase - cyanohydrin - nitroaldol - β-nitro alcohol - Henry reaction - enantioselectivity - enzyme engineering

• 1 Alvarez-Casao Y, Marques-Lopez E, Herrera RP. Symmetry 2011; 3: 220

• 2 Khan N.-uH, Kureshy RI, Abdi SHR, Agrawal S, Jasra RV. Coord. Chem. Rev. 2008; 252: 593

• 3 Palomo C, Oiarbide M, Laso A. Eur. J. Org. Chem. 2007; 2561

• 4 Shibasaki M, Kanai M, Matsunaga S, Kumagai N. Acc. Chem. Res. 2009; 42: 1117

• 5 Dadashipour M, Asano Y. ACS Catal. 2011; 1: 1121

• 6 Gruber-Khadjawi M, Fechter MH, Griengl H, Enzyme Catalysis in Organic Synthesis Drauz K, Gröger H, May O. Wiley VCH Weinheim, Germany 2012; 947

• 7 Lanfranchi E, Steiner K, Glieder A, Hajnal I, Sheldon RA, van Pelt S, Winkler M. Recent Pat. Biotechnol. 2013; 7: 197

• 8 Milner SE, Moody TS, Maguire AR. Eur. J. Org. Chem. 2012; 3059

• 9 Sharma M, Sharma NN, Bhalla TC. Enzyme Microb. Technol. 2005; 37: 279

• 10 Winkler M, Glieder A, Steiner K, Comprehensive Chirality Carreira EM, Yamamoto H. Elsevier Amsterdam 2012; 7. 350

• 11 Wöhler F, Liebig J. Ann. Pharm. (Lemgo, Ger.) 1837; 22: 1

• 12 Brovetto M, Gamenara D, Mendez PS, Seoane GA. Chem. Rev. 2011; 111: 4346

• 13 Fesko K, Gruber-Khadjawi M. ChemCatChem 2013; 5: 1248

• 14 Holt J, Hanefeld U. Curr. Org. Synth. 2009; 6: 15

• 15 Kara S, Liese A, Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology Flickinger MC. Wiley VCH Weinheim, Germany 2010; 2034

• 16 Purkarthofer T, Skranc W, Schuster C, Griengl H. Appl. Microbiol. Biotechnol. 2007; 76: 309

• 17 Rosenthaler L. Biochem. Z. 1908; 14: 238

• 18 Henry L. C. R. Hebd. Seances Acad. Sci. 1895; 120: 1265

• 19 Purkarthofer T, Gruber K, Gruber-Khadjawi M, Waich K, Skranc W, Mink D, Griengl H. Angew. Chem. Int. Ed. 2006; 45: 3454

• 20 Selmar D, Lieberei R, Biehl B, Conn EE. Physiol. Plant. 1989; 75: 97

• 21 Seigler DS, Herbivores: Their Interactions with Secondary Plant Metabolites Rosenthal GA, Berenbaum MR. Academic Press San Diego, CA 1991; 1. 35

• 22 Hajnal I, Łyskowski A, Hanefeld U, Gruber K, Schwab H, Steiner K. FEBS J. 2013; 280: 5815

• 23 Poulton JE. Plant Physiol. 1990; 94: 401

• 24 Zagrobelny M, Bak S, Møller BL. Phytochemistry 2008; 69: 1457

• 25 Sulzbacher Caruso C, de Fátima Travensolo R, de Campus Bicudo R, de Macedo Lemos EG, Ulian de Araújo AP, Carrilho E. Microb. Pathog. 2009; 47: 118

• 26 Andexer J, von Langermann J, Mell A, Bocola M, Kragl U, Eggert T, Pohl M. Angew. Chem. Int. Ed. 2007; 46: 8679

• 27 Pichersky E, Lewinsohn E. Ann. Rev. Plant Biol. 2011; 62: 549

• 28 Makrides SC. Microbiol. Rev. 1996; 60: 512

• 29 Cregg JM, Tolstorukov I, Kusari A, Sunga J, Madden K, Chappell T. Methods Enzymol. 2009; 463: 169

• 30 Näätsaari L, Mistlberger B, Ruth C, Hajek T, Hartner FS, Glieder A. PLoS One 2012; 7: e39 720

• 31 Semba H, Ichige E, Imanaka T, Atomi H, Aoyagi H. Appl. Microbiol. Biotechnol. 2008; 79: 563

• 32 Becker W, Eschenhof E, Pfeil E, Benthin U. Biochem. Z. 1963; 337: 156

• 33 Glieder A, Weis R, Skranc W, Pöchlauer P, Dreveny I, Majer S, Wubbolts M, Schwab H, Gruber K. Angew. Chem. Int. Ed. 2003; 42: 4815

• 34 Hasslacher M, Schall M, Hayn M, Griengl H, Kohlwein SD, Schwab H. J. Biol. Chem. 1996; 271: 5884

• 35 Hasslacher M, Schall M, Hayn M, Bona R, Rumbold K, Lückl J, Griengl H, Kohlwein SD, Schwab H. Protein Expression Purif. 1997; 11: 61

• 36 Klempier N, Griengl H, Hayn M. Tetrahedron Lett. 1993; 34: 4769

• 37 Dadashipour M, Fukuta Y, Asano Y. Protein Expression Purif. 2011; 77: 92

• 38 Hughes J, Decarvalho JPC, Hughes MA. Arch. Biochem. Biophys. 1994; 311: 496

• 39 Semba H, Dobashi Y, Matsui T. Biosci., Biotechnol., Biochem. 2008; 72: 1457

• 40 Bove C, Conn EE. J. Biol. Chem. 1961; 236: 207

• 41 Wajant H, Mundry KW, Pfizenmaier K. Plant Mol. Biol. 1994; 26: 735

• 42 Breithaupt H, Pohl M, Bönigk W, Heim P, Schimz KL, Kula MR. J. Mol. Catal. B: Enzym. 1999; 6: 315

• 43 Trummler K, Wajant H. J. Biol. Chem. 1997; 272: 4770

• 44 Trummler K, Roos J, Schwaneberg U, Effenberger F, Förster S, Pfizenmaier K, Wajant H. Plant Sci. (Shannon, Irel.) 1998; 139: 19

• 45 Fukuta Y, Nanda S, Kato Y, Yurimoto H, Sakai Y, Komeda H, Asano Y. Biosci., Biotechnol., Biochem. 2011; 75: 214

• 46 Dadashipour M, Yamazaki M, Momonoi K, Tamura K, Fuhshuku K.-i, Kanase Y, Uchimura E, Kaiyun G, Asano Y. J. Biotechnol. 2011; 153: 100

• 47 Ueatrongchit T, Komeda H, Asano Y. J. Mol. Catal. B: Enzym. 2009; 56: 208

• 48 Zhao GJ, Yang ZQ, Guo YH. J. Biosci. Bioeng. 2011; 112: 321

• 49 Asano Y, Tamura K, Doi N, Ueatrongchit T, Kittikun A, Ohmiya T. Biosci., Biotechnol., Biochem. 2005; 69: 2349

• 50 Hernández L, Luna H, Ruíz-Terán F, Vázquez A. J. Mol. Catal. B: Enzym. 2004; 30: 105

• 51 Hickel A, Heinrich G, Schwab H, Griengl H. Biotechnol. Tech. 1997; 11: 55

• 52 Pscheidt B, Avi M, Gaisberger R, Hartner FS, Skranc W, Glieder A. J. Mol. Catal. B: Enzym. 2008; 52–53: 183

• 53 Xu LL, Singh BK, Conn EE. Arch. Biochem. Biophys. 1986; 250: 322

• 54 Yemm RS, Poulton JE. Arch. Biochem. Biophys. 1986; 247: 440

• 55 Bhunya R, Mahapatra T, Nanda S. Tetrahedron: Asymmetry 2009; 20: 1526

• 56 Tükel SS, Yildirim D, Alagöz D, Alptekin Ö, Yücebilgic G, Bilgin R. J. Mol. Catal. B: Enzym. 2010; 66: 161

• 57 Lu WY, Chen P, Lin GQ. Tetrahedron 2008; 64: 7822

• 58 Alagöz D, Tükel SS, Yildirim D. J. Mol. Catal. B: Enzym. 2014; 101: 40

• 59 Gerstner E, Pfeil E. Hoppe-Seylerʼs Z. Physiol. Chem. 1972; 353: 271

• 60 Fang F, Ji A, Meng Z. React. Kinet. Catal. Lett. 2008; 93: 233

• 61 Kuroki GW, Conn EE. Proc. Natl. Acad. Sci. U. S. A. 1989; 86: 6978

• 62 Ueatrongchit T, Tamura K, Ohmiya T, Kittikun A, Asano Y. Enzyme Microb. Technol. 2010; 46: 456

• 63 Wajant H, Förster S, Selmar D, Effenberger F, Pfizenmaier K. Plant Physiol. 1995; 109: 1231

• 64 Han SQ, Ouyang PK, Wei P, Hu Y. Biotechnol. Lett. 2006; 28: 1909

• 65 Solis A, Luna H, Perez HI, Manjarrez N. Tetrahedron: Asymmetry 2003; 14: 2351

• 66 Solis A, Luna H, Manjarrez N, Perez HI. Tetrahedron 2004; 60: 10427

• 67 Pratush A, Sharma M, Seth A, Bhalla TC. J. Biochem. Technol. 2011; 3: 274

• 68 Hussain Z, Wiedner R, Steiner K, Hajek T, Avi M, Hecher B, Sessitsch A, Schwab H. Appl. Environ. Microbiol. 2012; 78: 2053

• 69 Becker W, Freund H, Pfeil E. Angew. Chem. Int. Ed. Engl. 1965; 4: 1079

• 70 Becker W, Pfeil E. J. Am. Chem. Soc. 1966; 88: 4299

• 71 Brussee J, Roos EC, van der Gen A. Tetrahedron Lett. 1988; 29: 4485

• 72 Brussee J, Loos WT, Kruse CG, van der Gen A. Tetrahedron 1990; 46: 979

• 73 Effenberger F, Ziegler T, Förster S. Angew. Chem. Int. Ed. Engl. 1987; 26: 458

• 74 Kiljunen E, Kanerva LT. Tetrahedron: Asymmetry 1996; 7: 1105

• 75 Chen PR, Han SQ, Lin GQ, Li ZY. J. Org. Chem. 2002; 67: 8251

• 76 Han SQ, Lin GQ, Li ZY. Tetrahedron: Asymmetry 1998; 9: 1835

• 77 Willeman WF, Straathof AJJ, Heijnen JJ. Enzyme Microb. Technol. 2002; 30: 200

• 78 Fechter MH, Gruber K, Avi M, Skranc W, Schuster C, Pöchlauer P, Klepp KO, Griengl H. Chem.–Eur. J. 2007; 13: 3369

• 79 Purkarthofer T, Gruber K, Fechter MH, Griengl H. Tetrahedron 2005; 61: 7661

• 80 Kiljunen E, Kanerva LT. Tetrahedron: Asymmetry 1997; 8: 1225

• 81 Albrecht J, Jansen I, Kula MR. Biotechnol. Appl. Biochem. 1993; 17: 191

• 82 Guterl J.-K, Andexer JN, Sehl T, von Langermann J, Frindi-Wosch I, Rosenkranz T, Fitter J, Gruber K, Kragl U, Eggert T, Pohl M. J. Biotechnol. 2009; 141: 166

• 83 Ritzen B, Hoekman S, Verdasco ED, van Delft FL, Rutjes FPJT. J. Org. Chem. 2010; 75: 3461

• 84 Ognyanov VI, Datcheva VK, Kyler KS. J. Am. Chem. Soc. 1991; 113: 6992

• 85 Tellitu I, Badía D, Domínguez E, García FJ. Tetrahedron: Asymmetry 1994; 5: 1567

• 86 Zandbergen P, van der Linden J, Brussee J, van der Gen A. Synth. Commun. 1991; 21: 1387

• 87 Han SQ, Chen PR, Lin GQ, Huang H, Li ZY. Tetrahedron: Asymmetry 2001; 12: 843

• 88 Schmidt M, Griengl H. Top. Curr. Chem. 1999; 200: 193

• 89 Bhunya R, Jana N, Das T, Nanda S. Synlett 2009; 1237

• 90 Cruz Silva MM, Sá e Melo ML, Parolin M, Tessaro D, Riva S, Danieli B. Tetrahedron: Asymmetry 2004; 15: 21

• 91 Effenberger F, Eichhorn J. Tetrahedron: Asymmetry 1997; 8: 469

• 92 Chen PR, Han SQ, Lin GQ, Huang H, Li ZY. Tetrahedron: Asymmetry 2001; 12: 3273

• 93 Nanda S, Kato Y, Asano Y. Tetrahedron 2005; 61: 10908

• 94 Ritzen B, van Oers MCM, van Delft FL, Rutjes FPJT. J. Org. Chem. 2009; 74: 7548

• 95 Warmerdam EGJC, van den Nieuwendijk AMCH, Brussee J, van der Gen A, Kruse CG. Recl. Trav. Chim. Pays-Bas 1996; 115: 20

• 96 Ziegler T, Hörsch B, Effenberger F. Synthesis 1990; 575

• 97 Monterde MI, Nazabadioko S, Rebolledo F, Brieva R, Gotor V. Tetrahedron: Asymmetry 1999; 10: 3449

• 98 de Gonzalo G, Brieva R, Gotor V. J. Mol. Catal. B: Enzym. 2002; 19: 223

• 99 Huuhtanen TT, Kanerva LT. Tetrahedron: Asymmetry 1992; 3: 1223

• 100 Nanda S, Kato Y, Asano Y. Tetrahedron: Asymmetry 2006; 17: 735

• 101 Avi M, Griengl H, Organic Synthesis with Enzymes in Non-Aqueous Media Carrea G, Riva S. Wiley VCH Weinheim (Germany) 2008; 211

• 102 Loos WT, Geluk HW, Ruijken MMA, Kruse CG, Brussee J, van der Gen A. Biocatal. Biotransform. 1995; 12: 255

• 103 Anderson NG. Org. Process Res. Dev. 2012; 16: 852

• 104 Effenberger F, Hörsch B, Weingart F, Ziegler T, Kühner S. Tetrahedron Lett. 1991; 32: 2605

• 105 Li N, Zong M.-H, Liu C, Peng H.-S, Wu H.-C. Biotechnol. Lett. 2003; 25: 219

• 106 Effenberger F, Roos J, Kobler C. Angew. Chem. Int. Ed. 2002; 41: 1876

• 107 North M. Tetrahedron: Asymmetry 2003; 14: 147

• 108 Roberge C, Fleitz F, Pollard D, Devine P. Tetrahedron: Asymmetry 2007; 18: 208

• 109 Kiljunen E, Kanerva LT. Tetrahedron: Asymmetry 1997; 8: 1551

• 110 Kobler C, Bohrer A, Effenberger F. Tetrahedron 2004; 60: 10397

• 111 Avi M, Fechter MH, Gruber K, Belaj F, Pöchlauer P, Griengl H. Tetrahedron 2004; 60: 10411

• 112 Li N, Zong M.-H, Peng H.-S, Wu H.-C, Liu C. J. Mol. Catal. B: Enzym. 2003; 22: 7

• 113 Huang S.-R, Liu S.-L, Zong M.-H, Xu R. Biotechnol. Lett. 2005; 27: 79

• 114 Liu S.-L, Zong M.-H, Huang S.-R. Biocatal. Biotransform. 2005; 23: 453

• 115 Purkarthofer T, Skranc W, Weber H, Griengl H, Wubbolts M, Scholz G, Pöchlauer P. Tetrahedron 2004; 60: 735

• 116 Luzzio FA. Tetrahedron 2001; 57: 915

• 117 Ono N. The Nitro Group in Organic Synthesis Wiley New York 2001;

• 118 Concellón JM, Rodríguez-Solla H, Concellón C. J. Org. Chem. 2006; 71: 7919

• 119 Ji YQ, Qi G, Judeh ZMA. Tetrahedron: Asymmetry 2011; 22: 929

• 120 Liu S.-L, Wolf C. Org. Lett. 2008; 10: 1831

• 121 Panov I, Drabina P, Padelkova Z, Simunek P, Sedlak M. J. Org. Chem. 2011; 76: 4787

• 122 Shibasaki M, Gröger H, Comprehensive Asymmetric Catalysis Jacobsen EN, Pfaltz A, Yamamoto H. Springer Heidelberg 1999; 3. 1075

• 123 Shibasaki M, Kanai M, Gröger H, Comprehensive Asymmetric Catalysis, Suppl. 1 Jacobsen EN, Pfaltz A, Yamamoto H. Springer Heidelberg 2004; 1. 131

• 124 Spangler KY, Wolf C. Org. Lett. 2009; 11: 4724

• 125 Trost BM, Yeh VSC. Angew. Chem. Int. Ed. 2002; 41: 861

• 126 Zhou YR, Dong JF, Zhang FL, Gong YF. J. Org. Chem. 2011; 76: 588

• 127 Li HM, Wang BM, Deng L. J. Am. Chem. Soc. 2006; 128: 732

• 128 Palomo C, Oiarbide M, Mielgo A. Angew. Chem. Int. Ed. 2004; 43: 5442

• 129 Palomo C, Oiarbide M, Laso A. Angew. Chem. Int. Ed. 2005; 44: 3881

• 130 Sohtome Y, Hashimoto Y, Nagasawa K. Eur. J. Org. Chem. 2006; 2894

• 131 Fuhshuku K.-i, Asano Y. J. Biotechnol. 2011; 153: 153

• 132 Busto E, Gotor-Fernández V, Gotor V. Org. Process Res. Dev. 2011; 15: 236

• 133 Tang R.-C, Guan Z, He Y.-H, Zhu W. J. Mol. Catal. B: Enzym. 2010; 63: 62

• 134 Wang J.-L, Li X, Xie H.-Y, Liu B.-K, Lin X.-F. J. Biotechnol. 2010; 145: 240

• 135 López-Iglesias M, Busto E, Gotor V, Gotor-Fernández V. Adv. Synth. Catal. 2011; 353: 2345

• 136 Le Z.-G, Guo L.-T, Jiang G.-F, Yang XB, Liu HQ. Green Chem. Lett. Rev. 2013; 6: 277

• 137 Gao N, Chen Y.-L, He Y.-H, Guan Z. RSC Adv. 2013; 3: 16850

• 138 Niedermeyer U, Kula MR. Angew. Chem. Int. Ed. Engl. 1990; 29: 386

• 139 Wajant H, Förster S. Plant Sci. (Shannon, Irel.) 1996; 115: 25

• 140 Griengl H, Hickel A, Johnson DV, Kratky C, Schmidt M, Schwab H. Chem. Commun. (Cambridge) 1997; 1933

• 141 Förster S, Roos J, Effenberger F, Wajant H, Sprauer A. Angew. Chem. Int. Ed. 1996; 35: 437

• 142 Bühler H, Effenberger F, Förster S, Roos J, Wajant H. ChemBioChem 2003; 4: 211

• 143 Schmidt M, Herve S, Klempier N, Griengl H. Tetrahedron 1996; 52: 7833

• 144 Effenberger F, Förster S, Wajant H. Curr. Opin. Biotechnol. 2000; 11: 532

• 145 Griengl H, Klempier N, Pöchlauer P, Schmidt M, Shi NY, Zabelinskaja-Mackova AA. Tetrahedron 1998; 54: 14477

• 146 Fröhlich RFG, Zabelinskaja-Mackova AA, Fechter MH, Griengl H. Tetrahedron: Asymmetry 2003; 14: 355

• 147 von Langermann J, Mell A, Paetzold E, Daußmann T, Kragl U. Adv. Synth. Catal. 2007; 349: 1418

• 148 Xu R, Zong M.-H, Liu Y.-Y, He J, Zhang Y.-Y, Lou W.-Y. Appl. Microbiol. Biotechnol. 2004; 66: 27

• 149 Gruber-Khadjawi M, Purkarthofer T, Skranc W, Griengl H. Adv. Synth. Catal. 2007; 349: 1445

• 150 Kazlauskas RJ. Book of Abstracts TuTech Innovation Hamburg, Germany 2012; 21

• 151 Padhi SK, Fujii R, Legatt GA, Fossum SL, Berchtold R, Kazlauskas RJ. Chem. Biol. 2010; 17: 863

• 152 Yuryev R, Purkarthofer T, Gruber M, Griengl H, Liese A. Biocatal. Biotransform. 2010; 28: 348

• 153 Yuryev R, Briechle S, Gruber-Khadjawi M, Griengl H, Liese A. ChemCatChem 2010; 2: 981

• 154 Effenberger F, Schwämmle A. Biocatal. Biotransform. 1996; 14: 167

• 155 Van Almsick A, Buddrus J, Hönicke-Schmidt P, Laumen K, Schneider MP. J. Chem. Soc., Chem. Commun. 1989; 1391

• 156 Inagaki M, Hiratake J, Nishioka T, Oda J. J. Am. Chem. Soc. 1991; 113: 9360

• 157 Fishman A, Zviely M. Tetrahedron: Asymmetry 1998; 9: 107

• 158 Mitsuda S, Yamamoto H, Umemura T, Hirohara H, Nabeshima S. Agric. Biol. Chem. 1990; 54: 2907

• 159 Effenberger F, Gutterer B, Ziegler T, Eckhardt E, Aichholz R. Liebigs Ann. Chem. 1991; 47

• 160 Gartler G, Kratky C, Gruber K. J. Biotechnol. 2007; 129: 87

• 161 Gruber K, Gugganig M, Wagner UG, Kratky C. Biol. Chem. 1999; 380: 993

• 162 Gruber K, Gartler G, Krammer B, Schwab H, Kratky C. J. Biol. Chem. 2004; 279: 20501

• 163 Schmidt A, Gruber K, Kratky C, Lamzin VS. J. Biol. Chem. 2008; 283: 21827

• 164 Wagner UG, Hasslacher M, Griengl H, Schwab H, Kratky C. Structure (Oxford, U. K.) 1996; 4: 811

• 165 Zuegg J, Gruber K, Gugganig M, Wagner UG, Kratky C. Protein Sci. 1999; 8: 1990

• 166 Lauble H, Decanniere K, Wajant H, Förster S, Effenberger F. Acta Crystallogr., Sect. D 1999; 55: 904

• 167 Lauble H, Miehlich B, Förster S, Wajant H, Effenberger F. Protein Sci. 2001; 10: 1015

• 168 Lauble H, Förster S, Miehlich B, Wajant H, Effenberger F. Acta Crystallogr., Sect. D 2001; 57: 194

• 169 Lauble H, Miehlich B, Förster S, Kobler C, Wajant H, Effenberger F. Protein Sci. 2002; 11: 65

• 170 Lauble H, Knödler S, Schindelin H, Förster S, Wajant H, Effenberger F. Acta Crystallogr., Sect. D 1996; 52: 887

• 171 Lauble H, Miehlich B, Förster S, Wajant H, Effenberger F. Biochemistry 2002; 41: 12043

• 172 Andexer JN, Staunig N, Eggert T, Kratky C, Pohl M, Gruber K. ChemBioChem 2012; 13: 1932

• 173 Dreveny I, Gruber K, Glieder A, Thompson A, Kratky C. Structure (Oxford, U. K.) 2001; 9: 803

• 174 Dreveny I, Andryushkova AS, Glieder A, Gruber K, Kratky C. Biochemistry 2009; 48: 3370

• 175 Lauble H, Müller K, Schindelin H, Förster S, Effenberger F. Proteins: Struct., Funct., Genet. 1994; 19: 343

• 176 Gruber K, Kratky C. J. Polym. Sci., Part A: Polym. Chem. 2004; 42: 479

• 177 Becker W, Pfeil E. Biochem. Z. 1965; 346: 301

• 178 Gruber K. Proteins: Struct., Funct., Bioinf. 2001; 44: 26

• 179 Hasslacher M, Kratky C, Griengl H, Schwab H, Kohlwein SD. Proteins: Struct., Funct., Bioinf. 1997; 27: 438

• 180 Bauer M, Griengl H, Steiner W. Biotechnol. Bioeng. 1999; 62: 20

• 181 Bauer M, Geyer R, Griengl H, Steiner W. Food Technol. Biotechnol. 2002; 40: 9

• 182 Łyskowski A, Steiner K, Hajnal I, Steinkellner G, Schwab H, Gruber K. Acta Crystallogr., Sect. F 2012; 68: 451

• 183 Steiner K, Schwab H. Comput. Struct. Biotechnol. J. 2012; 2: e201 209 010

• 184 Strohmeier GA, Pichler H, May O, Gruber-Khadjawi M. Chem. Rev. 2011; 111: 4141

• 185 Andexer J, Guterl J.-K, Pohl M, Eggert T. Chem. Commun. (Cambridge) 2006; 4201

• 186 Krammer B, Rumbold K, Tschemmernegg M, Pöchlauer P, Schwab H. J. Biotechnol. 2007; 129: 151

• 187 Pscheidt B, Liu ZB, Gaisberger R, Avi M, Skranc W, Gruber K, Griengl H, Glieder A. Adv. Synth. Catal. 2008; 350: 1943

• 188 Reisinger C, van Assema F, Schürmann M, Hussain Z, Remler P, Schwab H. J. Mol. Catal. B: Enzym. 2006; 39: 149

• 189 Avi M, Wiedner RM, Griengl H, Schwab H. Chem.–Eur. J. 2008; 14: 11415

• 190 Effenberger F, Wajant H, Lauble P, Förster S, Bühler H, Schwab H, Kratky C, Wagner U, Steiner E. US 6 319 697, 2001 Chem. Abstr.. 2000 132 191223

• 191 Yan G, Cheng S, Zhao G, Wu S, Liu Y, Sun W. Biotechnol. Lett. 2003; 25: 1041

• 192 Ichige E, Semba H, Shijuku T, Harayama S. US 7 531 330, 2009 Chem. Abstr.. 2005 143 381808

• 193 Asano Y, Dadashipour M, Yamazaki M, Doi N, Komeda H. Protein Eng., Des. Sel. 2011; 24: 607

• 194 Asano Y, Akiyama T, Yu F, Sato E. US 8 030 053, 2011 Chem. Abstr.. 2006 144 405868

• 195 Okrob D, Metzner J, Wiechert W, Gruber K, Pohl M. ChemBioChem 2012; 13: 797

• 196 Liu Z, Pscheidt B, Avi M, Gaisberger R, Hartner FS, Schuster C, Skranc W, Gruber K, Glieder A. ChemBioChem 2008; 9: 58

• 197 Weis R, Gaisberger R, Skranc W, Gruber K, Glieder A. Angew. Chem. Int. Ed. 2005; 44: 4700

• 198 Feichtenhofer S, Höffken WW, Schwab H Poster at Enzyme Engineering XX, Groningen, The Netherlands 2009

• 199 Effenberger F, Förster S, Wajant H. DE 19 963 485, 2001 Chem. Abstr.. 2001 135 45300

• 200 Bühler H, Miehlich B, Effenberger F. ChemBioChem 2005; 6: 711

• 201 Scholz KE, Kopka B, Wirtz A, Pohl M, Jaeger K.-E, Krauss U. Appl. Environ. Microbiol. 2013; 79: 4727

• 202 Gaisberger R, Weis R, Luiten R, Skranc W, Wubbolts M, Griengl H, Glieder A. J. Biotechnol. 2007; 129: 30

• 203 Andexer JN, Langermann JV, Kragl U, Pohl M. Trends Biotechnol. 2009; 27: 599

• 204 von Langermann J, Guterl J.-K, Pohl M, Wajant H, Kragl U. Bioprocess Biosyst. Eng. 2008; 31: 155

• 205 Hanefeld U. Chem. Soc. Rev. 2013; 42: 6308

• 206 Torrelo G, van Midden N, Stloukal R, Hanefeld U. ChemCatChem 2014; 6: 1096

• 207 Okrob D, Paravidino M, Orru RVA, Wiechert W, Hanefeld U, Pohl M. Adv. Synth. Catal. 2011; 353: 2399

• 208 Scholz KE, Okrob D, Kopka B, Grünberger A, Pohl M, Jaeger K.-E, Krauss U. Appl. Environ. Microbiol. 2012; 78: 5025

• 209 Sheldon RA, van Pelt S. Chem. Soc. Rev. 2013; 42: 6223

• 210 Chmura A, Rustler S, Paravidino M, van Rantwijk F, Stolz A, Sheldon RA. Tetrahedron: Asymmetry 2013; 24: 1225

• 211 Baum S, van Rantwijk F, Stolz A. Adv. Synth. Catal. 2012; 354: 113

• 212 Rustler S, Motejadded H, Altenbuchner J, Stolz A. Appl. Microbiol. Biotechnol. 2008; 80: 87

• 213 Sosedov O, Matzer K, Bürger S, Kiziak C, Baum S, Altenbuchner J, Chmura A, van Rantwijk F, Stolz A. Adv. Synth. Catal. 2009; 351: 1531

• 214 Rozzell JD, Enzyme Catalysis in Organic Synthesis Drauz K, Gröger H, May O. Wiley VCH Weinheim, Germany 2012; 1849