Skip to main content
Log in

Enzymes useful for chiral compound synthesis: structural biology, directed evolution, and protein engineering for industrial use

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Biocatalysts (enzymes) have many advantages as catalysts for the production of useful compounds as compared to chemical catalysts. The stereoselectivity of the enzymes is one advantage, and thus the stereoselective production of chiral compounds using enzymes is a promising approach. Importantly, industrial application of the enzymes for chiral compound production requires the discovery of a novel useful enzyme or enzyme function; furthermore, improving the enzyme properties through protein engineering and directed evolution approaches is significant. In this review, the significance of several enzymes showing stereoselectivity (quinuclidinone reductase, aminoalcohol dehydrogenase, old yellow enzyme, and threonine aldolase) in chiral compound production is described, and the improvement of these enzymes using protein engineering and directed evolution approaches for further usability is discussed. Currently, enzymes are widely used as catalysts for the production of chiral compounds; however, for further use of enzymes in chiral compound production, improvement of enzymes should be more essential, as well as discovery of novel enzymes and enzyme functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Baik SH, Yoshioka H, Yukawa H, Harayama S (2007) Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor A3(2). J Microbiol Biotechnol 17:721–727

    CAS  Google Scholar 

  • Brown BJ, Deng Z, Karplus PA, Massey V (1998) On the active site of old yellow enzyme. Role of histidine 191 and asparagine 194. J Biol Chem 273:32753–32762

    Article  CAS  PubMed  Google Scholar 

  • Dadashipur M, Ishida Y, Yamamoto K, Asano Y (2015) Discovery and molecular and biocatalytic properties of hydroxynitrile lyase from an invasive millipede, Chamberlinius hualienensis. Proc Natl Acad Sci U S A 112:10605–10610

    Article  Google Scholar 

  • di Salvo ML, Remesh SG, Vivoli M, Ghatge MS, Paiardini A, D’Aguanno S, Safo MK, Contestabile R (2014) On the catalytic mechanism and stereospecificity of Escherichia coli L-threonine aldolase. FEBS J. 281:129–145

    Article  PubMed  Google Scholar 

  • Dücker N, Baer K, Simon S, Gröger H, Hummel W (2010) Threonine aldolases—screening, properties and applications in the synthesis of non-proteinogenic β-hydroxy-α-amino acids. Appl Microbiol Biotechnol 88:409–424

  • Farina V, Reeves JT, Senanayake CH, Song JJ (2006) Asymmetric synthesis of active pharmaceutical ingredients. Chem Rev 106:2734–2793

    Article  CAS  PubMed  Google Scholar 

  • Guan L-J, Ohtsukal J, Okai M, Miyakawa T, Mase T, Zhi Y, Hou F, Ito N, Iwasaki A, Yasohara Y, Tanokura M (2015) A new target region for changing the substrate specificity of amine transaminases. Sci Rep 5:10753

    Article  CAS  PubMed  Google Scholar 

  • Gwon HJ, Baik SH (2010) Diasteroselective synthesis of L-threo-3,4-dihydroxyphenylserine by low-specific L-threonine aldolase mutants. Biotechnol Lett 32:143–149

    Article  CAS  PubMed  Google Scholar 

  • Hall M, Stueckler C, Ehammer H, Pointner E, Oberdorfer G, Gruber K, Hauer B, Stuermer R, Kroutil W, Macheroux P, Faber K (2008a) Asymmetric bioreduction of C=C bonds using enoate reductases POR1, OPR3 and YqjM: enzyme-based stereocontrol. Adv Synth Catal 350:411–418

    Article  CAS  Google Scholar 

  • Hall M, Stueckler C, Hauer B, Stuermer R, Friedrich T, Breuer M, Kroutil W, Faber K (2008b) Asymmetric bioreduction of activated C=C bonds using Zymomonas mobilis NCR enoate reductase and old yellow enzymes OYE 1-3 from yeasts. Eur J Org Chem 2008:1511–1516

    Article  Google Scholar 

  • Hibi M, Ogawa J (2014) Characteristics and biotechnology applications of aliphatic amino acid hydroxylases belonging to the Fe(II)/α-ketoglutarate-dependent dioxygenase superfamily. Appl Microbiol Biotechnol 98:3869–3876

    Article  CAS  PubMed  Google Scholar 

  • Horinouchi N, Ogawa J, Kawano T, Sakai T, Saito K, Matsumoto S, Sasaki M, Mikami Y, Shimizu S (2006a) One-pot microbial synthesis of 2′-deoxyribonucleoside from glucose, acetaldehyde, and a nucleobase. Biotechnol Lett 28:877–881

    Article  CAS  PubMed  Google Scholar 

  • Horinouchi N, Ogawa J, Kawano T, Sakai T, Saito K, Matsumoto S, Sasaki M, Mikami Y, Shimizu S (2006b) Efficient production of 2-deoxyribose 5-phosphate from glucose and acetoaldehyde by coupling of the alcoholic fermentation system of baker’s yeast and deoxyriboaldolase-expressing Escherichia coli. Biosci Biotechnol Biochem 70:1371–1378

    Article  CAS  PubMed  Google Scholar 

  • Horinouchi N, Sakai T, Kawano T, Matsumoto S, Sasaki M, Hibi M, Shima J, Shimizu S, Ogawa J (2012) Construction of microbial platform for an energy-requiring bioprocess: practical 2′-deoxyribonucleoside production involving a C-C coupling reaction with high energy substrates. Microb Cell Factories 11:82

    Article  CAS  Google Scholar 

  • Horita S, Kataoka M, Kitamura N, Nakagawa T, Miyakawa T, Ohtsuka J, Nagata K, Shimizu S, Tanokura M (2015) An engineered old yellow enzyme that enables efficient synthesis of (4R,6R)-actinol in a one-pot reduction system. Chembiochem 16:440–445

    Article  CAS  PubMed  Google Scholar 

  • Hou F, Miyakawa T, Kataoka M, Takeshita D, Kumashiro S, Uzura A, Urano N, Nagata K, Shimizu S, Tanokura M (2014) Structural basis for high substrate-binding affinity and enantioselectivity of 3-quinuclidinone reductase AtQR. Biochem Biophys Res Commun 446:911–915

    Article  CAS  PubMed  Google Scholar 

  • Isotani K, Kurokawa J, Itoh N (2012) Production of (R)-3-quinuclidinol by E. coli biocatalysts possessing NADH-dependent 3-quinuclidinone reductase (QNR and bacC) from Microbacterium luteolum and Leifsonia alcohol dehydrogenase (LSADH). Int J Mol Sci 13:13542–13552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isotani K, Kurokawa J, Suzuki F, Nomoto S, Negishi T, Matsuda M, Itoh N (2013) Gene cloning and characterization of two NADH-dependent 3-quinuclidinone reductases from Microbacterium luteolum JCM 9174. Appl Environ Microbiol 79:1378–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jennewein S, Schürmann M, Wolberg M, Hilker I, Luiten R, Wubbolts M, Mink D (2006) Directed evolution of an industrial biocatalyst: 2-deoxy-D-ribose 5-phosphate aldolase. Biotechnol J 1:537–548

    Article  CAS  PubMed  Google Scholar 

  • Jörnvall H, Persson B, Krrok M, Atrian S, Gonzàlez-Duarte R, Jefery J, Ghosh D (1995) Short-chain dehydrogenase/reductase (SDR). Biochemistry 34:6003–6013

    Article  PubMed  Google Scholar 

  • Kataoka M, Shimizu K, Sakamoto K, Yamada H, Shimizu S (1995a) Optical resolution of racemic pantolactone with a novel fungal enzyme, lactonohydrolase. Appl Microbiol Biotechnol 43:974–977

    Article  CAS  Google Scholar 

  • Kataoka M, Shimizu K, Sakamoto K, Yamada H, Shimizu S (1995b) Lactonohydrolase-catalyzed optical resolution of pantoyl lactone: selection of a potent enzyme producer and optimization of culture and reaction conditions for practical resolution. Appl Microbiol Biotechnol 44:333–338

    Article  CAS  Google Scholar 

  • Kataoka M, Wada M, Nishi K, Yamada H, Shimizu S (1997a) Purification and characterization of L-allo-threonine aldolase from Aeromonas jandaei DK-39. FEMS Microbiol Lett 151:245–248

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Ikemi M, Morikawa T, Miyoshi T, Nishi K, Wada M, Yamada H, Shimizu S (1997b) Isolation and characterization of D-threonine aldolase, a pyridoxal-5′-phosphate-dependent enzyme from Arthrobacter sp. DK-38. Eur J Biochem 248:385–393

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Kotaka A, Hasegawa A, Wada M, Yoshizumi A, Nakamori S, Shimizu S (2002) Old yellow enzyme from Candida macedoniensis catalyzes stereospecific reduction of C=C bond of ketoisophorone. Biosci Biotechnol Biochem 66:2651–2657

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Kita K, Wada M, Yasohara Y, Hasegawa J, Shimizu S (2003) Novel bioreduction system for the production of chiral alcohols. Appl Microbiol Biotechnol 62:437–445

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Kotaka A, Thiwthong R, Wada M, Nakamori S, Shimizu S (2004) Cloning and overexpression of the old yellow enzyme gene of Candida macedoniensis, and its application to the production of a chiral compound. J Biotechnol 114:1–9

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Nakamura Y, Urano N, Ishige T, Shi G, Kita S, Sakamoto K, Shimizu S (2006) A novel NADP+-dependent L-1-amino-2-propanol dehydrogenase from Rhodococcus erythropolis MAK154: a promising enzyme for the production of double chiral aminoalcohols. Lett Appl Microbiol 43:430–435

    Article  CAS  PubMed  Google Scholar 

  • Kataoka M, Ishige T, Urano N, Nakamura Y, Sakuradani E, Fukui S, Kita S, Sakamoto K, Shimizu S (2008) Cloning and expression of the L-1-amino-2-propanol dehydrogenase gene from Rhodococcus erythropolis, and its application to double chiral compound production. Appl Microbiol Biotechnol 80:597–604

    Article  CAS  PubMed  Google Scholar 

  • Kielkopf CL, Burley SK (2002) X-ray structures of threonine aldolase complexes: structural basis of substrate recognition. Biochemistry 41:11711–11720

    Article  CAS  PubMed  Google Scholar 

  • Kohli RM, Massey V (1998) The oxidative half-reaction of old yellow enzyme. The role of tyrosine 196. J Biol Chem 273:32763–32770

    Article  CAS  PubMed  Google Scholar 

  • Kolet SP, Jadhav DD, Priyadarshini B, Swarge BN, Thulasiram HV (2014) Fungi mediated production and practical purification of (R)-3-quinuclidinol. Tetrahedron Lett 55:5911–5914

    Article  CAS  Google Scholar 

  • Liu JQ, Nagata S, Dairi T, Misono H, Shimizu S, Yamada H (1997a) The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific L-threonine aldolase that catalyzes cleavage of L-allo-threonine and L-threonine to glycine: expression of the gene in Escherichia coli and purification and characterization of the enzyme. Eur J Biochem 245:289–293

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Dairi T, Kataoka M, Shimizu S, Yamada H (1997b) L-allo-threonine aldolase from Aeromonas jandaei DK-39: Gene cloning, nucleotide sequencing, and identification of the pyridoxal 5′-phosphate-binding lysine residue by site-directed mutagenesis. J Bacteriol 179:3555–3560

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu JQ, Dairi T, Ito N, Kataoka M, Shimizu S, Yamada H (1998a) Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity L-threonine aldolase from Escherichia coli. Eur J Biochem 255:220–226

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Ito S, Dairi T, Ito N, Kataoka M, Shimizu S, Yamada H (1998b) Gene cloning, nucleotide sequencing, and purification and characterization of the low-specificity L-threonine aldolase from Pseudomonas sp. strain NCIMB 10558. Appl Environ Microbiol 64:549–554

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu JQ, Dairi T, Ito N, Kataoka M, Shimizu S, Yamada H (1998c) A novel metal-activated pyridoxal enzyme with a unique primary structure, low specificity D-threonine aldolase from Arthrobacter sp. strain DK-38. J Biol Chem 273:16678–16685

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Ito S, Dairi T, Itoh N, Shimizu S, Yamada H (1998d) Low-specificity L-threonine aldolase of Pseudomonas sp. NCIMB 10558: purification, characterization and its application to β-hydroxy-α-amino acid synthesis. Appl Microbiol Biotechnol 49:702–708

    Article  CAS  Google Scholar 

  • Liu JQ, Odani M, Dairi T, Itoh N, Shimizu S, Yamada H (1999) A new route to L-threo-3-[4-(methylthio)phenylserine], a key intermediate for the synthesis of antibiotics: recombinant low-specificity D-threonine aldolase-catalyzed stereospecific resolution. Appl Microbiol Biotechnol 51:586–591

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Odani M, Yasuoka M, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (2000) Gene cloning and overproduction of low-specificity D-threonine aldolase from Alcaligenes xylosoxidans and its application for production of a key intermediate for parkinsonism drug. Appl Microbiol Biotechnol 54:44–51

    Article  CAS  PubMed  Google Scholar 

  • Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S (2003) A novel enzyme, D-3-hydroxyaspartate aldolase from Paracoccus denitrificans IFO 13301: purification, characterization, and gene cloning. Appl Microbiol Biotechnol 62:53–60

    Article  CAS  PubMed  Google Scholar 

  • Mikami M, Korenaga T, Ohkuma T, Noyori R (2000) Asymmetric activation/deactivation of racemic Ru catalysis for highly enantioselective hydrogenation of ketonic substrates. Angew Chem Int Ed Eng 39:3707–3710

    Article  CAS  Google Scholar 

  • Misono H, Maeda H, Tuda K, Ueshima S, Miyazaki N, Nagata S (2005) Characterization of an iducible phenylserine aldolase from Pseudomonas putida 24-1. Appl Environ Microbiol 71:4602–4609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitsukura K, Suzuki M, Tada K, Yoshida T, Nagasawa T (2010) Asymmetric synthesis of chiral cyclic amine from cyclic imine by bacterial whole-cell catalyst of enantioselective imine reductase. Org Biomol Chem 8:4533–4535

    Article  CAS  PubMed  Google Scholar 

  • Mitsukura K, Suzuki M, Shinoda S, Kuramot T, Yoshida T, Nagasawa T (2011) Purification and characterization of a novel (R)-imine reductase from Streptomyces sp. GF3587. Biosci Biotechnol Biochem 75:1778–1782

    Article  CAS  PubMed  Google Scholar 

  • Nomoto F, Hirayama Y, Ikunaka M, Inoue T, Otsuka K (2003) A practical chemoenzymatic process to access (R)-quinuclidin-3-ol on scale. Tetrahedron Asymmetry 14:1871–1877

    Article  CAS  Google Scholar 

  • Noyori R, Ohkuma T (2001) Asymmetric catalysis by architectural and functional molecular engineering: practical chemo- and stereoselective hydrogenation of ketones. Angew Chem Int Ed Eng 40:40–73

    Article  CAS  Google Scholar 

  • Ogawa J, Shimizu S (1997) Diversity and versatility of microbial hydantoin-transforming enzymes. J Mol Catal B Enzym 2:163–176

    Article  CAS  Google Scholar 

  • Padhi SK, Bougioukou DJ, Stewart JD (2009) Site-saturation mutagenesis of tryptophan 116 of Saccharomyces pastorianus old yellow enzyme uncovers stereocomplementary variants. J Am Chem Soc 131:3271–3280

    Article  CAS  PubMed  Google Scholar 

  • Persson B, Krrok M, Jörnvall H (1991) Characteristics of short-chain alcohol dehydrogenases and related enzymes. Eur J Biochem 200:537–543

    Article  CAS  PubMed  Google Scholar 

  • Qin HM, Imai FL, Miyakawa T, Kataoka M, Kitamura N, Urano N, Mori K, Kawabata H, Okai M, Ohtsuka J, Hou F, Nagata K, Shimizu S, Tanokura M (2014) L-allo-threonine aldolase with an H128Y/S292R mutation from Aeromonas jandaei DK-39 reveals the structural basis of changes in substrate stereoselectivity. Acta Crystallogr D Biol Crystallogr 70:1695–1703

    Article  CAS  PubMed  Google Scholar 

  • Reß T, Hummel W, Hanlon SP, Iding H, Gröger H (2015) The organic-synthetic potential of recombinant ene reductases: substrate-scope evaluation and process optimization. ChemCatChem 7:1302–1311

    Article  Google Scholar 

  • Richter N, Gröger H, Hummel W (2011) Asymmetric reduction of activated alkenes using an enoate reductase from Gluconobacter oxydans. Appl Microbiol Biotechnol 89:79–89

    Article  CAS  PubMed  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

    Article  CAS  Google Scholar 

  • Rustler S, Motejadded H, Altenbuchner J, Stolz A (2008) Simultaneous expression of an arylactonitrilase from Pseudomonas fluorescens and a (S)-oxynitrilase from Manihot esculenta in Pichia pastoris for the synthesis od (S)-mandelic acid. Appl Microbiol Biotechnol 80:87–97

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto K, Honda K, Wada K, Kita S, Tsuzaki K, Nose H, Kataoka M, Shimizu S (2005) Practical resolution system for DL-pantoyl lactone using the lactonase from Fusarium oxysporum. J Biotechnol 118:99–106

    Article  CAS  PubMed  Google Scholar 

  • Savile CK, Janey JM, Mundorff EC, Moore JC, Tam S, Jarvis WR, Colbeck JC, Krebber A, Fleitz FJ, Brands J, Devine PN, Huisman GW, Hughes GJ (2010) Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science 329:305–309

    Article  CAS  PubMed  Google Scholar 

  • Shimada Y, Yasuda S, Takahashi M, Hayashi T, Miyazawa N, Sato I, Abiru Y, Uchiyama S, Hishigaki H (2010) Cloning and expression of a novel NAD(P)H-dependent daidzein reductase, an enzyme involved in the metabolism of daidzein, from equol-producing Lactococcus strain 20-92. Appl Environ Microbiol 76:5892–5901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinreiber J, Fesko K, Reisinger C, Schürmann M, van Assema F, Wolberg M, Mink D, Griengl H (2007) Threonine aldolases—an emerging tool for organic synthesis. Tetrahedron 63:918–926

    Article  CAS  Google Scholar 

  • Sternbach LH, Kaiser S (1952) Antispasmodics. I. Bicyclic basic alcohols. J Am Chem Soc 74:2215–2218

    Article  CAS  Google Scholar 

  • Stuermer R, Hauer B, Hall M, Faber K (2007) Asymmetric bioreduction of activated C=C bonds using enoate reductases from the old yellow enzyme family. Curr Opin Chem Biol 11:203–213

    Article  CAS  PubMed  Google Scholar 

  • Takeshita D, Kataoka M, Miyakawa T, Miyazono K, Kumashiro S, Nagai T, Urano N, Uzura A, Nagata K, Shimizu S, Tanokura M (2014) Structural basis of stereospecific reduction by quinuclidinone reductase. AMB Express 4:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Toogood HS, Gardiner JM, Scrutton NS (2010) Biocatalytic reductions and chemical versatility of the old yellow enzyme family of flavoprotein oxidoreductases. ChemCatChem 2:892–914

    Article  CAS  Google Scholar 

  • Tsuji N, Honda K, Wada M, Okano K, Ohtake H (2014) Isolation and characterization of a thermotolerant ene reductase from Geobacillus sp. 30 and its heterologous expression in Rhodococcus opacus. Appl Microbiol Biotechnol 98:5925–5935

    Article  CAS  PubMed  Google Scholar 

  • Uhl MK, Oberdorfer G, Steinkellner G, Riegler-Berket L, Mink D, van Assema F, Schürmann M, Gruber K (2015) The crystal structure of D-threonine aldolase from Alcaligenes xylosoxidans provides insight into a metal ion assisted PLP-dependent mechanism. PLoS One 10:e0124056

    Article  PubMed  PubMed Central  Google Scholar 

  • Urano N, Kataoka M, Ishige T, Kita S, Sakamoto K, Shimizu S (2011a) Genetic analysis around aminoalcohol dehydrogenase gene of Rhodococcus erythropolis MAK154: a putative GntR transcription factor in transcriptional regulation. Appl Microbiol Biotechnol 89:739–746

    Article  CAS  PubMed  Google Scholar 

  • Urano N, Fukui S, Kumashiro S, Ishige T, Kita S, Sakamoto K, Kataoka M, Shimizu S (2011b) Directed evolution of an aminoalcohol dehydrogenase for efficient production of double chiral aminoalcohols. J Biosci Bioeng 111:266–271

    Article  CAS  PubMed  Google Scholar 

  • Uzura A, Nomoto F, Sakoda A, Nishimoto Y, Kataoka M, Shimizu S (2009) Stereoselective synthesis of (R)-3-quinuclidinol through asymmetric reduction of 3-quinuclidinone with 3-quinuclidinone reductase of Rhodotorula rubra. Appl Microbiol Biotechnol 83:617–626

  • Wada M, Yoshizumi A, Noda Y, Kataoka M, Shimizu S, Takagi H, Nakamori S (2003) Production of a doubly chiral compound, (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone, by two-step enzymatic asymmetric reduction. Appl Environ Microbiol 69:933–937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Li J, Wu Q, Zhu D (2013) Microbial stereospecific reduction of 3-quinuclidinone with newly isolated Nocardia sp. and Rhodococcus erythropolis. J Mol Catal B Enzym 88:14–19

    Article  CAS  Google Scholar 

  • Winkler CK, Tasnádi G, Clay D, Hall M, Faber K (2012) Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds. J Biotechnol 162:381–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada H, Shimizu S, Shimada H, Tani Y, Takahashi S, Ohashi T (1980) Production of D-phenylglycine-related amino acids by immobilized microbial cells. Biochemie 62:395–399

    Article  CAS  Google Scholar 

  • Yoshizumi A, Wada M, Takagi H, Shimizu S, Nakamori S (2001) Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding monovalent cation-activated levodione reductase from Corynebacterium aquaticum M-13. Biosci Biotechnol Biochem 65:830–836

    Article  Google Scholar 

  • Zhang WX, Xu GC, Huang L, Pan J, Yu HL, Xu JH (2013) Highly efficient synthesis of (R)-3-quinuclidinol in a space-time yield of 916 g L−1 d−1 using a new bacterial reductase ArQR. Org Lett 15:4917–4919

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This review included the results obtained by the Targeted Proteins Research Program (TPRP) of the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michihiko Kataoka.

Ethics declarations

Ethical approval

This article does not contain studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kataoka, M., Miyakawa, T., Shimizu, S. et al. Enzymes useful for chiral compound synthesis: structural biology, directed evolution, and protein engineering for industrial use. Appl Microbiol Biotechnol 100, 5747–5757 (2016). https://doi.org/10.1007/s00253-016-7603-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-016-7603-8

Keywords

Navigation