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2000
Volume 22, Issue 1
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646
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Abstract

Biocatalysis has emerged as a transformative technology in pharmaceutical synthesis, enabling efficient and sustainable production of chiral bioactive compounds. This review focuses on recent advancements in biocatalytic methods, highlighting key enzyme systems, such as ketoreductases, aminotransferases, and imine reductases, which facilitate the synthesis of chiral alcohols, amines, and other pharmaceutical intermediates with high enantiomeric purity. Directed evolution and protein engineering have significantly enhanced enzyme stability, activity, and substrate specificity, broadening their applications in industrial-scale drug production. For example, ketoreductases have been successfully applied in the synthesis of intermediates for drugs, such as enalapril and duloxetine, while engineered transaminases enable efficient production of sitagliptin. Beyond asymmetric reduction and transamination, advancements in C-H bond activation using enzymes like P450 monooxygenases and unspecific peroxygenases provide new opportunities for regioselective functionalization. Additionally, multienzyme cascade reactions and chemo-biocatalytic approaches integrate multiple catalytic steps into single processes, reducing reaction complexity and waste while enhancing efficiency. These innovations highlight the growing role of biocatalysis in green chemistry, offering a sustainable alternative to traditional chemical synthesis methods. As the field advances with contributions from bioinformatics, artificial intelligence, and high-throughput techniques, biocatalysis is poised to drive further innovation in pharmaceutical manufacturing, fostering environmentally friendly processes and scalable solutions for complex drug synthesis. This review underscores the critical impact of biocatalysis in shaping the future of sustainable chemistry and its pivotal role in addressing the growing demand for greener pharmaceutical technologies.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. SheldonR.A. Green chemistry and resource efficiency: Towards a green economy.Green Chem.201618113180318310.1039/C6GC90040B
     [Google Scholar]
  2. KoenigS.G. DillonB. Driving toward greener chemistry in the pharmaceutical industry.Curr. Opin. Green Sustain. Chem.20177565910.1016/j.cogsc.2017.07.004
     [Google Scholar]
  3. PatelR. Biocatalysis: Synthesis of chiral intermediates for pharmaceuticals.Curr. Org. Chem.200610111289132110.2174/138527206777698011
     [Google Scholar]
  4. YoussefS. StüveO. PatarroyoJ.C. RuizP.J. RadosevichJ.L. HurE.M. BravoM. MitchellD.J. SobelR.A. SteinmanL. ZamvilS.S. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease.Nature20024206911788410.1038/nature01158 12422218
     [Google Scholar]
  5. WiviottS.D. BraunwaldE. McCabeC.H. MontalescotG. RuzylloW. GottliebS. NeumannF.J. ArdissinoD. De ServiS. MurphyS.A. RiesmeyerJ. WeerakkodyG. GibsonC.M. AntmanE.M. Prasugrel versus clopidogrel in patients with acute coronary syndromes.N. Engl. J. Med.2007357202001201510.1056/NEJMoa0706482 17982182
     [Google Scholar]
  6. GreenJ.B. BethelM.A. ArmstrongP.W. BuseJ.B. EngelS.S. GargJ. JosseR. KaufmanK.D. KoglinJ. KornS. LachinJ.M. McGuireD.K. PencinaM.J. StandlE. SteinP.P. SuryawanshiS. Van de WerfF. PetersonE.D. HolmanR.R. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med.2015373323224210.1056/NEJMoa1501352 26052984
     [Google Scholar]
  7. SperlJ.M. SieberV. Multienzyme cascade reactions status and recent advances.ACS Catal.2018832385239610.1021/acscatal.7b03440
     [Google Scholar]
  8. PatelR.N. Biocatalysis: Synthesis of key intermediates for development of pharmaceuticals.ACS. Catal.2011191056107410.1021/cs200219b
     [Google Scholar]
  9. de SouzaR.O.M.A. MirandaL.S.M. BornscheuerU.T. A retrosynthesis approach for biocatalysis in organic synthesis.Chemistry20172350120401206310.1002/chem.201702235 28514518
     [Google Scholar]
  10. RudroffF. MihovilovicM.D. GrögerH. SnajdrovaR. IdingH. BornscheuerU.T. Opportunities and challenges for combining chemo and biocatalysis.Nat. Catal.201811122210.1038/s41929‑017‑0010‑4
     [Google Scholar]
  11. NiY. XuJ.H. Biocatalytic ketone reduction: A green and efficient access to enantiopure alcohols.Biotechnol. Adv.20123061279128810.1016/j.biotechadv.2011.10.007 22079798
     [Google Scholar]
  12. XuG. ZhangY. WangY. NiY. Genome hunting of carbonyl reductases from Candida glabrata for efficient preparation of chiral secondary alcohols.Bioresour. Technol.201824755356010.1016/j.biortech.2017.09.111 28978494
     [Google Scholar]
  13. HouX. ZhangH. ChenB.C. GuoZ. SinghA. GoswamiA. GilmoreJ.L. SheppeckJ.E. DyckmanA.J. CarterP.H. MathurA. Regioselective epoxide ring opening for the stereospecific scale-up synthesis of BMS-960, a potent and selective isoxazole-containing S1P1 receptor agonist.Org. Process Res. Dev.201721220020710.1021/acs.oprd.6b00366
     [Google Scholar]
  14. GuoX. TangJ.W. YangJ.T. NiG.W. ZhangF.L. ChenS.X. Development of a practical enzymatic process for preparation of (S)-2-chloro-1-(3,4-difluorophenyl)ethanol.Org. Process Res. Dev.201721101595160110.1021/acs.oprd.7b00230
     [Google Scholar]
  15. LiangJ. LalondeJ. BorupB. MitchellV. MundorffE. TrinhN. KochrekarD.A. Nair CheratR. PaiG.G. Development of a biocatalytic process as an alternative to the (−)-DIP-Cl-mediated asymmetric reduction of a key intermediate of montelukast.Org. Process Res. Dev.201014119319810.1021/op900272d
     [Google Scholar]
  16. ModukuruN.K. SukumaranJ. CollierS.J. ChanA.S. GohelA. HuismanG.W. KeledjianR. NarayanaswamyK. NovickS.J. PalanivelS.M. SmithD. WeiZ. WongB. YeoW.L. EntwistleD.A. Development of a practical, biocatalytic reduction for the manufacture of (S)-licarbazepine using an evolved] ketoreductase.Org. Process Res. Dev.201418681081510.1021/op4003483
     [Google Scholar]
  17. LarikF.A. SaeedA. ChannarP.A. MehfoozH. Stereoselective synthetic approaches towards (S)-duloxetine: 2000 to date.Tetrahedron Asymmetry20162722-231101111210.1016/j.tetasy.2016.09.007
     [Google Scholar]
  18. RenZ.Q. LiuY. PeiX.Q. WangH.B. WuZ.L. Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15.J. Mol. Catal., B Enzym.2015113768110.1016/j.molcatb.2015.01.008
     [Google Scholar]
  19. RimoldiI. FacchettiG. NavaD. ContenteM.L. GandolfiR. Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra.Tetrahedron Asymmetry2016279-1038939610.1016/j.tetasy.2016.04.002
     [Google Scholar]
  20. FryszkowskaA. PetersonJ. DaviesN.L. DewarC. EvansG. BycroftM. TriggsN. FlemingT. GorantlaS.S.C. HogeG. QuirmbachM. TimmannaU. Reddy PoreddyS. Kumar ReddyD.N. DahanukarV. Holt-TiffinK.E. Development of a chemoenzymatic process for dehydroepiandrosterone acetate synthesis.Org. Process Res. Dev.20162081520152810.1021/acs.oprd.6b00215
     [Google Scholar]
  21. ChenX. LiuZ.Q. HuangJ.F. LinC.P. ZhengY.G. Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy-butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli.Chem. Commun. (Camb.)20155161123281233110.1039/C5CC04652A 26140446
     [Google Scholar]
  22. XuF. KosjekB. CabirolF.L. ChenH. DesmondR. ParkJ. GohelA.P. CollierS.J. SmithD.J. LiuZ. JaneyJ.M. ChungJ.Y.L. AlvizoO. Synthesis of vibegron enabled by a ketoreductase rationally designed for high pH dynamic kinetic reduction.Angew. Chem. Int. Ed.201857236863686710.1002/anie.201802791 29689604
     [Google Scholar]
  23. HughesD.L. Biocatalysis in drug development-highlights of] the recent patent literature.Org. Process Res. Dev.20182291063108010.1021/acs.oprd.8b00232
     [Google Scholar]
  24. NealonC.M. MusaM.M. PatelJ.M. PhillipsR.S. Controlling substrate specificity and stereospecificity of alcohol dehydrogenases.ACS Catal.2015542100211410.1021/cs501457v
     [Google Scholar]
  25. YouZ.N. ChenQ. ShiS.C. ZhengM.M. PanJ. QianX.L. LiC.X. XuJ.H. Switching cofactor dependence of] 7β-hydroxysteroid dehydrogenase for cost-effective production of ursodeoxycholic acid.ACS Catal.20199146647310.1021/acscatal.8b03561
     [Google Scholar]
  26. GongX.M. QinZ. LiF.L. ZengB.B. ZhengG.W. XuJ.H. Development of an engineered ketoreductase with simultaneously improved thermostability and activity for making a bulky atorvastatin precursor.ACS Catal.20199114715310.1021/acscatal.8b03382
     [Google Scholar]
  27. ZhengG.W. LiuY.Y. ChenQ. HuangL. YuH.L. LouW.Y. LiC.X. BaiY.P. LiA.T. XuJ.H. Preparation of structurally diverse chiral alcohols by engineering ketoreductase CgKR1.ACS Catal.20177107174718110.1021/acscatal.7b01933
     [Google Scholar]
  28. QinF. QinB. MoriT. WangY. MengL. ZhangX. JiaX. AbeI. YouS. Engineering of Candida glabrata ketoreductase L for asymmetric reduction of α-halo ketones.ACS Catal.2016696135614010.1021/acscatal.6b01552
     [Google Scholar]
  29. QinF. QinB. ZhangW. LiuY. SuX. ZhuT. OuyangJ. GuoJ. LiY. ZhangF. TangJ. JiaX. YouS. Discovery of a switch between prelog and anti-prelog reduction toward halogen-substituted acetophenones in short-chain dehydrogenase/reductases.ACS Catal.2018876012602010.1021/acscatal.8b00807
     [Google Scholar]
  30. GhislieriD. TurnerN.J. Biocatalytic approaches to the synthesis of enantiomerically pure chiral amines.Top. Catal.201457528430010.1007/s11244‑013‑0184‑1
     [Google Scholar]
  31. KellyS.A. PohleS. WharryS. MixS. AllenC.C.R. MoodyT.S. GilmoreB.F. Application of ω-transaminases in the pharmaceutical industry.Chem. Rev.2018118134936710.1021/acs.chemrev.7b00437 29251912
     [Google Scholar]
  32. SavileC.K. JaneyJ.M. MundorffE.C. MooreJ.C. TamS. JarvisW.R. ColbeckJ.C. KrebberA. FleitzF.J. BrandsJ. DevineP.N. HuismanG.W. HughesG.J. Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture.Science2010329598930530910.1126/science.1188934 20558668
     [Google Scholar]
  33. HöhneM. SchätzleS. JochensH. RobinsK. BornscheuerU.T. Rational assignment of key motifs for function guides in silico enzyme identification.Nat. Chem. Biol.201061180781310.1038/nchembio.447 20871599
     [Google Scholar]
  34. TelzerowA. ParisJ. HåkanssonM. González-SabínJ. Ríos-LombardíaN. SchürmannM. GrögerH. MorísF. KouristR. SchwabH. SteinerK. Amine transaminase from Exophiala xenobiotica-crystal structure and engineering of a fold IV transaminase that naturally converts biaryl ketones.ACS Catal.2019921140114810.1021/acscatal.8b04524
     [Google Scholar]
  35. PavlidisI.V. WeißM.S. GenzM. SpurrP. HanlonS.P. WirzB. IdingH. BornscheuerU.T. Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines.Nat. Chem.20168111076108210.1038/nchem.2578 27768108
     [Google Scholar]
  36. AbrahamsonM.J. Vázquez-FigueroaE. WoodallN.B. MooreJ.C. BommariusA.S. Development of an amine dehydrogenase for synthesis of chiral amines.Angew. Chem. Int. Ed.201251163969397210.1002/anie.201107813 22396126
     [Google Scholar]
  37. AbrahamsonM.J. WongJ.W. BommariusA.S. The evolution of an amine dehydrogenase biocatalyst for the asymmetric production of chiral amines.Adv. Synth. Catal.201335591780178610.1002/adsc.201201030
     [Google Scholar]
  38. YeL.J. TohH.H. YangY. AdamsJ.P. SnajdrovaR. LiZ. Engineering of amine dehydrogenase for asymmetric reductive amination of ketone by evolving Rhodococcus phenylalanine dehydrogenase.ACS Catal.2015521119112210.1021/cs501906r
     [Google Scholar]
  39. ChenF.F. ZhengG.W. LiuL. LiH. ChenQ. LiF.L. LiC.X. XuJ.H. Reshaping the active pocket of amine dehydrogenases for asymmetric synthesis of bulky aliphatic amines.ACS Catal.2018832622262810.1021/acscatal.7b04135
     [Google Scholar]
  40. XueY.P. CaoC.H. ZhengY.G. Enzymatic asymmetric synthesis of chiral amino acids.Chem. Soc. Rev.20184741516156110.1039/C7CS00253J 29362736
     [Google Scholar]
  41. Mangas-SanchezJ. FranceS.P. MontgomeryS.L. AlekuG.A. ManH. SharmaM. RamsdenJ.I. GroganG. TurnerN.J. Imine reductases (IREDs).Curr. Opin. Chem. Biol.201737192510.1016/j.cbpa.2016.11.022 28038349
     [Google Scholar]
  42. SchellerP.N. NestlB.M. The biochemical characterization of three imine-reducing enzymes from Streptosporangium roseum DSM43021, Streptomyces turgidiscabies and Paenibacillus elgii.Appl. Microbiol. Biotechnol.201610024105091052010.1007/s00253‑016‑7740‑0 27464826
     [Google Scholar]
  43. WetzlD. GandM. RossA. MüllerH. MatzelP. HanlonS.P. MüllerM. WirzB. HöhneM. IdingH. Asymmetric] reductive amination of ketones catalyzed by imine reductases.Chem. Cat. Chem. 20168122023202610.1002/cctc.201600384
     [Google Scholar]
  44. AlekuG.A. FranceS.P. ManH. Mangas-SanchezJ. MontgomeryS.L. SharmaM. LeipoldF. HussainS. GroganG. TurnerN.J. A reductive aminase from Aspergillus oryzae.Nat. Chem.201791096196910.1038/nchem.2782 28937665
     [Google Scholar]
  45. LiuW. MaH. LuoJ. ShenW. XuX. LiS. HuY. HuangH. Efficient synthesis of l-tert-leucine through reductive amination using leucine dehydrogenase and formate dehydrogenase coexpressed in recombinant E. coli.Biochem. Eng. J.20149120420910.1016/j.bej.2014.08.003
     [Google Scholar]
  46. RobinsonB.S. RiccardiK.A. GongY. GuoQ. StockD.A. BlairW.S. TerryB.J. DeminieC.A. DjangF. ColonnoR.J. LinP. BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.Antimicrob. Agents Chemother.20004482093209910.1128/AAC.44.8.2093‑2099.2000 10898681
     [Google Scholar]
  47. PoordadF. McConeJ.Jr BaconB.R. BrunoS. MannsM.P. SulkowskiM.S. JacobsonI.M. ReddyK.R. GoodmanZ.D. BoparaiN. DiNubileM.J. SniukieneV. BrassC.A. AlbrechtJ.K. BronowickiJ.P. Boceprevir for untreated chronic HCV genotype 1 infection.N. Engl. J. Med.2011364131195120610.1056/NEJMoa1010494 21449783
     [Google Scholar]
  48. HansonR.L. JohnstonR.M. GoldbergS.L. ParkerW.L. GoswamiA. Enzymatic preparation of an R-amino acid intermediate for a γ-secretase inhibitor.Org. Process Res. Dev.201317469370010.1021/op400013e
     [Google Scholar]
  49. CabirolF. L. CollierS. J. DaussmannT. ModukuruN. K. Processes using amino acid dehydrogenases and ketoreductase-based cofactor regenerating system.WO Patent 2011US241022011
  50. ZhangY.H. ChenF.F. LiB.B. ZhouX.Y. ChenQ. XuJ.H. ZhengG.W. Stereocomplementary synthesis of pharmaceutically relevant chiral 2-aryl-substituted pyrrolidines using imine reductases.Org. Lett.20202293367337210.1021/acs.orglett.0c00802 32281800
     [Google Scholar]
  51. KumarR. KarmilowiczM.J. BurkeD. BurnsM.P. ClarkL.A. ConnorC.G. CordiE. DoN.M. DoyleK.M. HoaglandS. LewisC.A. ManganD. MartinezC.A. McInturffE.L. MeldrumK. PearsonR. SteflikJ. RaneA. WeaverJ. Biocatalytic reductive amination from discovery to commercial manufacturing applied to abrocitinib JAK1 inhibitor.Nat. Catal.20214977578210.1038/s41929‑021‑00671‑5
     [Google Scholar]
  52. ChenF.F. HeX.F. ZhuX.X. ZhangZ. ShenX.Y. ChenQ. XuJ.H. TurnerN.J. ZhengG.W. Discovery of an imine reductase for reductive amination of carbonyl compounds with sterically challenging amines.J. Am. Chem. Soc.202314574015402510.1021/jacs.2c11354 36661845
     [Google Scholar]
  53. ZhangJ. MaY. ZhuF. BaoJ. WuQ. GaoS.S. CuiC. Structure-guided semi-rational design of an imine reductase for enantio-complementary synthesis of pyrrolidinamine.Chem. Sci. (Camb.)202314164265427210.1039/D2SC07014F 37123194
     [Google Scholar]
  54. FreyR. HayashiT. BullerR.M. Directed evolution of carbon–hydrogen bond activating enzymes.Curr. Opin. Biotechnol.201960293810.1016/j.copbio.2018.12.004 30583278
     [Google Scholar]
  55. RenataH. WangZ.J. ArnoldF.H. Expanding the enzyme universe: Accessing non-natural reactions by mechanism-guided directed evolution.Angew. Chem. Int. Ed.201554113351336710.1002/anie.201409470 25649694
     [Google Scholar]
  56. ZhangK. ShaferB.M. DemarsM.D.II SternH.A. FasanR. Controlled oxidation of remote sp3 C-H bonds in artemisinin via P450 catalysts with fine-tuned regio- and stereoselectivity.J. Am. Chem. Soc.201213445186951870410.1021/ja3073462 23121379
     [Google Scholar]
  57. KilleS. ZillyF.E. AcevedoJ.P. ReetzM.T. Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution.Nat. Chem.20113973874310.1038/nchem.1113 21860465
     [Google Scholar]
  58. HammerS.C. KubikG. WatkinsE. HuangS. MingesH. ArnoldF.H. Anti-Markovnikov alkene oxidation by metal-oxo–mediated enzyme catalysis.Science2017358636021521810.1126/science.aao1482 29026041
     [Google Scholar]
  59. ZhouH. WangB. WangF. YuX. MaL. LiA. ReetzM.T. Chemo- and regioselective dihydroxylation of benzene to hydroquinone enabled by engineered cytochrome P450 monooxygenase.Angew. Chem. Int. Ed.201958376476810.1002/anie.201812093 30511432
     [Google Scholar]
  60. ZhangR.K. HuangX. ArnoldF.H. Selective C-H bond functionalization with engineered heme proteins: New tools to generate complexity.Curr. Opin. Chem. Biol.201949677510.1016/j.cbpa.2018.10.004 30343008
     [Google Scholar]
  61. ZhangX. King-SmithE. RenataH. Total synthesis of tambromycin by combining chemocatalytic and biocatalytic C-H functionalization.Angew. Chem. Int. Ed.201857185037504110.1002/anie.201801165 29481729
     [Google Scholar]
  62. ZwickC.R.III RenataH. Remote C-H hydroxylation by] an α-ketoglutarate-dependent dioxygenase enables efficient] chemoenzymatic synthesis of manzacidin C and proline analogs.J. Am. Chem. Soc.201814031165116910.1021/jacs.7b12918 29283572
     [Google Scholar]
  63. BormannS. Gomez BaraibarA. NiY. HoltmannD. HollmannF. Specific oxyfunctionalisations catalysed by peroxygenases:] Opportunities, challenges and solutions.Catal. Sci. Technol.2015542038205210.1039/C4CY01477D
     [Google Scholar]
  64. HofrichterM. UllrichR. Oxidations catalyzed by fungal peroxygenases.Curr. Opin. Chem. Biol.20141911612510.1016/j.cbpa.2014.01.015 24607599
     [Google Scholar]
  65. Gomez de SantosP. CañellasM. TievesF. YounesS.H.H. Molina-EspejaP. HofrichterM. HollmannF. GuallarV. AlcaldeM. Selective synthesis of the human drug metabolite 5′-hydroxypropranolol by an evolved self-sufficient peroxygenase.ACS Catal.2018864789479910.1021/acscatal.8b01004
     [Google Scholar]
  66. BalkeK. BeierA. BornscheuerU.T. Hot spots for the protein engineering of Baeyer-Villiger monooxygenases.Biotechnol. Adv.201836124726310.1016/j.biotechadv.2017.11.007 29174001
     [Google Scholar]
  67. BongY. K. ClayM. D. CollierS. J. MijtsB. VogelM. ZhangX. ZhuJ. NazorJ. SmithD. SongS. Synthesis of prazole compounds.WO Patent 2010US593982011
     [Google Scholar]
  68. LathamJ. BrandenburgerE. ShepherdS.A. MenonB.R.K. MicklefieldJ. Development of halogenase enzymes for use in synthesis.Chem. Rev.2018118123226910.1021/acs.chemrev.7b00032 28466644
     [Google Scholar]
  69. GkotsiD.S. DhaliwalJ. McLachlanM.M.W. MulholandK.R. GossR.J.M. Halogenases: Powerful tools for biocatalysis (mechanisms applications and scope).Curr. Opin. Chem. Biol.20184311912610.1016/j.cbpa.2018.01.002 29414530
     [Google Scholar]
  70. AndorferM.C. ParkH.J. Vergara-CollJ. LewisJ.C. Directed evolution of RebH for catalyst-controlled halogenation of indole C–H bonds.Chem. Sci. (Camb.)2016763720372910.1039/C5SC04680G 27347367
     [Google Scholar]
  71. Cheung-LeeW.L. KolevJ.N. McIntoshJ.A. GilA.A. PanW. XiaoL. VelásquezJ.E. GangamR. WinstonM.S. LiS. AbeK. AlwediE. DanceZ.E.X. FanH. HiragaK. KimJ. KosjekB. LeD.N. MarzijaraniN.S. MatternK. McMullenJ.P. NarsimhanK. VikramA. WangW. YanJ.X. YangR.S. ZhangV. ZhongW. DiRoccoD.A. MorrisW.J. MurphyG.S. MaloneyK.M. Engineering hydroxylase activity, selectivity, and stability for a scalable concise synthesis of a key intermediate to belzutifan.Angew. Chem. Int. Ed.20246313e20231613310.1002/anie.202316133 38279624
     [Google Scholar]
  72. RiccaE. BrucherB. SchrittwieserJ.H. Multi-enzymatic cascade reactions: Overview and perspectives.Adv. Synth. Catal.2011353132239226210.1002/adsc.201100256
     [Google Scholar]
  73. BothP. BuschH. KellyP.P. MuttiF.G. TurnerN.J. FlitschS.L. Whole-cell biocatalysts for stereoselective C-H amination reactions.Angew. Chem. Int. Ed.20165541511151310.1002/anie.201510028 26689856
     [Google Scholar]
  74. FranceS.P. HussainS. HillA.M. HepworthL.J. HowardR.M. MulhollandK.R. FlitschS.L. TurnerN.J. One-pot cascade synthesis of mono- and disubstituted piperidines and pyrrolidines using carboxylic acid reductase (CAR), ω-transaminase] (ω-TA), and imine reductase (IRED) biocatalysts.ACS Catal.2016663753375910.1021/acscatal.6b00855
     [Google Scholar]
  75. ZhouY. WuS. LiZ. Cascade biocatalysis for sustainable asymmetric synthesis: From biobased L-phenylalanine to high-value chiral chemicals.Angew. Chem. Int. Ed.20165538116471165010.1002/anie.201606235 27512928
     [Google Scholar]
  76. ChuaboonL. WongnateT. PunthongP. KiattiseweeC. LawanN. HsuC.Y. LinC.H. BornscheuerU.T. ChaiyenP. One-pot bioconversion of L-arabinose to L-ribulose in an enzymatic cascade.Angew. Chem. Int. Ed.20195882428243210.1002/anie.201814219 30605256
     [Google Scholar]
  77. MuttiF.G. KnausT. ScruttonN.S. BreuerM. TurnerN.J. Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades.Science201534962551525152910.1126/science.aac9283 26404833
     [Google Scholar]
  78. PayerS.E. PollakH. SchmidbauerB. HammF. JuričićF. FaberK. GlueckS.M. Multienzyme one-pot cascade for the stereoselective hydroxyethyl functionalization of substituted phenols.Org. Lett.201820175139514310.1021/acs.orglett.8b02058 30110168
     [Google Scholar]
  79. RulliG. DuangdeeN. BaerK. HummelW. BerkesselA. GrögerH. Direction of kinetically versus thermodynamically controlled organocatalysis and its application in chemoenzymatic synthesis.Angew. Chem. Int. Ed.201150347944794710.1002/anie.201008042 21744441
     [Google Scholar]
  80. MaG. XuZ. ZhangP. LiuJ. HaoX. OuyangJ. LiangP. YouS. JiaX. A novel synthesis of rasagiline via a chemoenzymatic dynamic kinetic resolution.Org. Process Res. Dev.201418101169117410.1021/op500152g
     [Google Scholar]
  81. Qing CaiS. Feng WangR. Wei YangX. Mei MaC. Nong LiJ. ShoyamaY. A bioactive alkaloid from the flowers of Trollius chinensis.Heterocycles20046361443144810.3987/COM‑04‑10062
     [Google Scholar]
  82. ZhaoJ. LichmanB.R. WardJ.M. HailesH.C. One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline analogues.Chem. Commun. (Camb.)201854111323132610.1039/C7CC08024G 29345260
     [Google Scholar]
  83. McIntoshJ.A. LiuZ. AndresenB.M. MarzijaraniN.S. MooreJ.C. MarshallN.M. Borra-GarskeM. ObligacionJ.V. FierP.S. PengF. ForstaterJ.H. WinstonM.S. AnC. ChangW. LimJ. HuffmanM.A. MillerS.P. TsayF.R. AltmanM.D. LesburgC.A. SteinhuebelD. TrotterB.W. CummingJ.N. NorthrupA. BuX. MannB.F. BibaM. HiragaK. MurphyG.S. KolevJ.N. MakarewiczA. PanW. FarasatI. BadeR.S. StoneK. DuanD. AlvizoO. AdpressaD. GuetschowE. HoytE. RegaladoE.L. CastroS. RiveraN. SmithJ.P. WangF. CrespoA. VermaD. AxnandaS. DanceZ.E.X. DevineP.N. TschaenD. CanadaK.A. BulgerP.G. SherryB.D. TruppoM.D. RuckR.T. CampeauL.C. BennettD.J. HumphreyG.R. CamposK.R. MaddessM.L. A kinase-cGAS cascade to synthesize a therapeutic sting activator.Nature2022603790143944410.1038/s41586‑022‑04422‑9 35296845
     [Google Scholar]
/content/journals/cbc/10.2174/0115734072375983250116103300
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Application of Biocatalysis in the Synthesis of Bioactive Compounds
Curr. Bioact. Compd. 22, E15734072375983 (2026); https://doi.org/10.2174/0115734072375983250116103300
/content/journals/cbc/10.2174/0115734072375983250116103300
/content/journals/cbc/10.2174/0115734072375983250116103300
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  • Article Type:     Review Article
Keyword(s): biocatalytic reaction; C-H activation; Chiral pharmaceuticals; direct evolution; multi-enzymatic cascade reaction; pharmaceutical technologies

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