Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2019 ; Vol.29-11: 1769~1776

AuthorZhi-Qiang Ren, Yan Liu, Xiao-Qiong Pei, Zhong-Liu Wu
Place of dutyKey Laboratory of Environmental and Applied Microbiology, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China,Schoolof Bioengineering, Sichuan University of Science & Engineering, Zigong 643000, China ,Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu 610041,China
TitleStereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoateusing theshort-chain dehydrogenase/reductaseChKRED12
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-11
AbstractEthyl (S)-3-hydroxy-3-(2-thienyl)propanoate((S)-HEES)acts as a key chiral intermediate for the blockbuster antidepressant drug duloxetine, which canbe achieved viathe stereoselective bioreduction ofethyl 3-oxo-3-(2-thienyl) propanoate (KEES) that containsa 3-oxoacyl structure.The sequences of the short-chain dehydrogenase/reductases from Chryseobacteriumsp. CA49 were analyzed, and the putative3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectivelycatalyze theNADPH-dependent reduction to produce(S)-HEES.The reductase activityof ChKRED12towardsothersubstrates with 3-oxoacyl structurewereconfirmed with excellent stereoselectivity (>99%ee) in most cases.When coupled with a cofactor recycling systemusingglucose dehydrogenase, the ChKRED12was able to catalyze the complete conversion of 100 g/LKEES within 12h, yielding the enantiopure product with>99% ee, showing a remarkablepotential to produce(S)-HEES.
Full-Text
Key_wordBioreduction, 3-oxoacyl-acyl-carrier-protein reductase, Short chain dehydrogenase, Duloxetine
References
  1. Balke K, Kadow M, Mallin H, Sass S, Bornscheuer UT. 2012. Discovery, application and protein engineering of BaeyerVilliger monooxygenases for organic synthesis. Org. Biomol. Chem. 10: 6249-6265.
    Pubmed CrossRef
  2. Bornscheuer UT, Huisman GW, Kazlauskas RJ, Lutz S, Moore JC, Robins K. 2012. Engineering the third wave of biocatalysis. Nature 485: 185-194.
    Pubmed CrossRef
  3. Deshpande PP, Nanduri VB, Pullockaran A, Christie H, Mueller RH, Patel RN. 2008. Microbial hydroxylation of obromophenylacetic acid: synthesis of 4-substituted-2, 3dihydrobenzofurans. J. Ind. Microbiol. Biotechnol. 35: 901-906.
    Pubmed CrossRef
  4. Hollmann F, Arends IW, Holtmann D. 2011. Enzymatic reductions for the chemist. Green Chem. 13: 2285-2314.
    CrossRef
  5. Ni Y, Xu J-H. 2012. Biocatalytic ketone reduction: a green and efficient access to enantiopure alcohols. Biotechnol. Adv. 30: 1279-1288.
    Pubmed CrossRef
  6. Ren Z-Q, Liu Y, Pei X-Q, Wang H-B, Wu Z-L. 2015. Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15. J. Mol. Catal. B Enzym. 113: 76-81.
    CrossRef
  7. Tang C-G, Lin H, Zhang C, Liu Z-Q, Yang T, Wu Z-L. 2011. Highly enantioselective bioreduction of N-methyl-3-oxo-3(thiophen-2-yl) propanamide for the production of (S)duloxetine. Biotechnol. Lett. 33: 1435-1440.
    Pubmed CrossRef
  8. Wada M, Yoshizumi A, Furukawa Y, Kawabata H, Ueda M, Takagi H, et al. 2004. Cloning and overexpression of the Exiguobacterium sp. F42 gene encoding a new short chain dehydrogenase, which catalyzes the stereoselective reduction of ethyl 3-oxo-3-(2-thienyl) propanoate to ethyl (S)-3-hydroxy3-(2-thienyl) propanoate. Biosci. Biotechnol. Biochem. 68: 1481-1488.
    Pubmed CrossRef
  9. Liu H, Hoff BH, Anthonsen T. 2000. Chemo-enzymatic synthesis of the antidepressant duloxetine and its enantiomer. Chirality 12: 26-29.
    CrossRef
  10. Bymaster F, Beedle E, Findlay J, Gallagher P, Krushinski J, Mitchell S, et al. 2003. Duloxetine (Cymbalta™), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg. Med. Chem. Lett. 13: 4477-4480.
    Pubmed CrossRef
  11. Deeter J, Frazier J, Staten G, Staszak M, Weigel L. 1990. Asymmetric synthesis and absolute stereochemistry of LY248686. Tetrahedron Lett. 31: 7101-7104.
    CrossRef
  12. Nakamura K, Yamanaka R, Matsuda T, Harada T. 2003. Recent developments in asymmetric reduction of ketones with biocatalysts. Tetrahedron Asymmetry 14: 2659-2681.
    CrossRef
  13. 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. 76: 249-255.
    Pubmed CrossRef
  14. Sun T, Li B, Nie Y, Wang D, Xu Y. 2017. Enhancement of asymmetric bioreduction of N,N-dimethyl-3-keto-3-(2-thienyl)1-propanamine to corresponding (S)-enantiomer by fusion of carbonyl reductase and glucose dehydrogenase. Bioresour. Bioprocess. 4: 21.
    CrossRef
  15. Toomey RE, Wakil SJ. 1966. Studies on the mechanism of fatty acid synthesis. XVI. Preparation and general properties of acyl-malonyl acyl carrier protein-condensing enzyme from Escherichia coli. J. Biol. Chem. 241: 1159-1165.
  16. Fisher M, Kroon JTM, Martindale W, Stuitje AR, Slabas AR, Rafferty JB. 2000. The X-ray structure of Brassica napus βketo acyl carrier protein reductase and its implications for substrate binding and catalysis. Structure 8: 339-347.
    CrossRef
  17. Birge CH, Vagelos PR. 1972. Acyl carrier protein. XVI. Intermediate reactions of unsaturated fatty acid synthesis in Escherichia coli and studies of fab B mutants. J. Biol. Chem. 247: 4921-4929.
  18. Prelog V. 1964. Specification of the stereospecificity of some oxidoreductases by diamond lattice sections. Pure Appl. Chem. 9: 12.
    CrossRef
  19. Huisman GW, Liang J, Krebber A. 2010. Practical chiral alcohol manufacture using ketoreductases. Curr. Opin. Chem. Biol. 14: 122-129.
    Pubmed CrossRef
  20. Tasnádi G, Hall M. 2013. Relevant practical applications of bioreduction processes in the synthesis of active pharmaceutical ingredients. Synth. Methods Biol. Act. Mol. 329-374.
    CrossRef
  21. Liu Y, Tang T-X, Pei X-Q, Zhang C, Wu Z-L. 2014. Identification of ketone reductase ChKRED20 from the genome of Chryseobacterium sp. CA49 for highly efficient anti-Prelog reduction of 3, 5-bis (trifluoromethyl) acetophenone. J. Mol. Catal. B Enzym. 102: 1-8.
    CrossRef
  22. Ratovelomanana-Vidal V, Girard C, Touati R, Tranchier J, Hassine BB, Genêt J. 2003. Enantioselective hydrogenation of β-keto esters using chiral diphosphine-ruthenium complexes:optimization for academic and industrial purposes and synthetic applications. Adv. Synth. Catal. 345: 261-274.
    CrossRef
  23. Takehara J, Qu JP, Kanno K, Kawabata H, Dekishima Y, Ueda M, et al. 2004. 3-Hydroxy-3-(2-Thienyl)Propionamide Compound, Process For Producing The Same, And Process For Producing 3-Amino-1-(2-Thienyl)-1-Propanol Compound Therefrom.
  24. Boulet SL, Filla SA, Gallagher PT, Hudziak KJ, Johansson AM, Karanjawala RE, et al. 2004. Propanamine derivatives as serotonin and norepinephrine reuptake inhibitors.
  25. Jung J, Park HJ, Uhm KN, Kim D, Kim HK. 2010. Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxy butanoate using a Saccharomyces cerevisiae reductase: enantioselectivity and enzyme-substrate docking studies. Biochim. Biophys. Acta 1804: 1841-1849.
    Pubmed CrossRef
  26. Oppermann U, Filling C, Hult M, Shafqat N, Wu X, Lindh M, et al. 2003. Short-chain dehydrogenases/reductases (SDR):the 2002 update. Chem. Biol. Interact. 143-144: 247-253.
    CrossRef
  27. Duax WL, Huether R, Pletnev V, Umland TC, Weeks CM. 2009. Divergent evolution of a Rossmann fold and identification of its oldest surviving ancestor. Int. J. Bioinform. Res. Appl. 5: 280-294.
    Pubmed CrossRef
  28. Keller B, Volkmann A, Wilckens T, Moeller G, Adamski J. 2006. Bioinformatic identification and characterization of new members of short-chain dehydrogenase/reductase superfamily. Mol. Cell. Endocrinol. 248: 56-60.
    Pubmed CrossRef
  29. Kallberg Y, Oppermann U, Jornvall H, Persson B. 2002. Short-chain dehydrogenase/reductase (SDR) relationships: a large family with eight clusters common to human, animal, and plant genomes. Protein Sci. 11: 636-641.
    Pubmed CrossRef Pubmed Central
  30. Rafferty JB, Simon JW, Baldock C, Artymiuk PJ, Baker PJ, Stuitje AR, et al. 1995. Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase. Structure 3: 927-938.
    CrossRef
  31. Shimakata T, Stumpf PK. 1982. Purification and characterizations of beta-Ketoacyl-[acyl-carrier-protein] reductase, betahydroxyacyl-[ acyl-carrier-protein] dehydrase, and enoyl-[acylcarrierprotein] reductase from Spinacia oleracea leaves. Arch. Biochem. Biophys. 218: 77-91.
    CrossRef
  32. Kavanagh KL, Jornvall H, Persson B, Oppermann U. 2008. Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell. Mol. Life Sci. 65: 3895-3906.
    Pubmed CrossRef Pubmed Central
  33. Kim TS, Patel SK, Selvaraj C, Jung WS, Pan CH, Kang YC, et al. 2016. A highly efficient sorbitol dehydrogenase from Gluconobacter oxydans G624 and improvement of its stability through immobilization. Sci. Rep. 6: 33438.
    Pubmed CrossRef Pubmed Central
  34. Cui D, Zhang L, Yao Z, Liu X, Lin J, Yuan YA, et al. 2013. Computational design of short-chain dehydrogenase Gox2181 for altered coenzyme specificity. J. Biotechnol. 167: 386-392.
    Pubmed CrossRef
  35. Sheldon PS, Kekwick RG, Smith CG, Sidebottom C, Slabas AR. 1992. 3-Oxoacyl-[ACP] reductase from oilseed rape (Brassica napus). Biochim. Biophys. Acta 1120: 151-159.
    CrossRef
  36. Fisher M, Kroon JT, Martindale W, Stuitje AR, Slabas AR, Rafferty JB. 2000. The X-ray structure of Brassica napus beta-keto acyl carrier protein reductase and its implications for substrate binding and catalysis. Structure 8: 339-347.
    CrossRef
  37. Ramachandran P, Jagtap SS, Patel SKS, Li J, Chan Kang Y, Lee J-K. 2016. Role of the non-conserved amino acid asparagine 285 in the glycone-binding pocket of Neosartorya fischeri β-glucosidase. RSC Adv. 6: 48137-48144.
    CrossRef
  38. Selvaraj C, Krishnasamy G, Jagtap SS, Patel SKS, Dhiman SS, Kim T-S, et al. 2016. Structural insights into the binding mode of d-sorbitol with sorbitol dehydrogenase using QMpolarized ligand docking and molecular dynamics simulations. Biochem. Eng. J. 114: 244-256.
    CrossRef
  39. Cai P, An M, Xu L, Xu S, Hao N, Li Y, et al. 2012. Development of a substrate-coupled biocatalytic process driven by an NADPH-dependent sorbose reductase from Candida albicans for the asymmetric reduction of ethyl 4chloro-3-oxobutanoate. Biotechnol. Lett. 34: 2223-2227.
    Pubmed CrossRef
  40. Wang LJ, Li CX, Ni Y, Zhang J, Liu X, Xu JH. 2011. Highly efficient synthesis of chiral alcohols with a novel NADHdependent reductase from Streptomyces coelicolor. Bioresour. Technol. 102: 7023-7028.
    Pubmed CrossRef
  41. Zhao FJ, Pei XQ, Ren ZQ, Wu ZL. 2016. Rapid asymmetric reduction of ethyl 4-chloro-3-oxobutanoate using a thermostabilized mutant of ketoreductase ChKRED20. Appl. Microbiol. Biotechnol. 100: 3567-3575.
    Pubmed CrossRef
  42. Brem J, Liljeblad A, Paizs C, Toşa MI, Irimie F-D, Kanerva LT. 2011. Lipases A and B from Candida antarctica in the enantioselective acylation of ethyl 3-heteroaryl-3hydroxypropanoates: aspects on the preparation and enantiopreference. Tetrahedron Asymmetry. 22: 315-322.
    CrossRef
  43. Soni P, Banerjee U. 2005. Biotransformations for the production of the chiral drug (S)-Duloxetine catalyzed by a novel isolate of Candida tropicalis. Appl. Microbiol. Biotechnol. 67: 771-777.
    Pubmed CrossRef



Copyright © 2009 by the Korean Society for Microbiology and Biotechnology.
All right reserved. Mail to jmb@jmb.or.kr
Online ISSN: 1738-8872    Print ISSN: 1017-7825    Powered by INFOrang Co., Ltd