Journal of Pharmaceutical Research
DOI: https://doi.org/10.18579/jopcr/v25.i2.37
Year: 2026, Volume: 25, Issue: 2, Pages: 68-84
Review Article
Sachin K Bhosale1, Sakshi Rajesh Singh1, Nirmala V Shinde2*, Yogesh V Ushir2
1Department of Pharmaceutical Chemistry, SMBT College of Pharmacy (Affiliated to Savitribai Phule Pune University, Pune), Dhamangaon, Nashik, Maharashtra, India
2Department of Pharmacognosy, SMBT College of Pharmacy (Affiliated to Savitribai Phule Pune University, Pune), Dhamangaon, Nashik, Maharashtra, India
*Corresponding Author
Email: [email protected]
Biocatalysis, which combines green chemistry and white biotechnology, provides a sustainable alternative to conventional chemical synthesis. Enzymes and microbial systems act as selective, renewable catalysts, enabling complex reactions under mild conditions with minimal waste and high atom economy. In pharmaceuticals and fine chemicals, biocatalysis supports shorter synthetic routes, improved stereoselectivity, and regulatory compliance. Advances in enzyme engineering, such as directed evolution, rational design, and machine learning, have expanded the capabilities and robustness of biocatalysts. Techniques such as enzyme immobilization and whole-cell catalysis enhance stability and cost efficiency. Case studies, including simvastatin and pregabalin synthesis, showcase its practical benefits. The integration of chemoenzymatic strategies merges enzymatic precision with chemical versatility, streamlining synthesis. Aligned with the 12 principles of green chemistry, biocatalysis reduces hazardous reagents, lowers energy use, and enables renewable feedstocks. As regulatory bodies promote greener practices, its industrial adoption grows. Future directions include AI-guided enzyme discovery and continuous flow systems for scalable, eco-friendly production. This review explores the current landscape, key innovations, and future directions of biocatalysis in sustainable chemical manufacturing.
Keywords: Biocatalysis; Green Chemistry, White Biotechnology, Enzyme Engineering, Sustainable Synthesis, Biotransformation, Eco-friendly Catalysis
1. Okpara MO. Microbial Enzymes and Their Applications in Food Industry: A Mini-Review. Advances in Enzyme Research. 2022; 10 (01). Available from: https://doi.org/10.4236/aer.2022.101002
2. Sheldon RA. Biocatalysis and Green Chemistry. Green Biocatalysis. Wiley. 2016; Available from: https://doi.org/10.1002/9781118828083.ch1
3. Hughes G, Lewis JC. Introduction: Biocatalysis in Industry. Chemical Reviews. 2018; 118 (1). Available from: https://doi.org/10.1021/acs.chemrev.7b00741
4. Phintha A, Chaiyen P. Rational and mechanistic approaches for improving biocatalyst performance. Chem Catalysis. 2022; 2 (10). Available from: https://doi.org/10.1016/j.checat.2022.09.026
5. Yi D, Bayer T, Badenhorst CPS, Wu S, Doerr M, Höhne M, et al. Recent trends in biocatalysis. Chemical Society Reviews. Royal Society of Chemistry. 2021; 50 (14). Available from: https://doi.org/10.1039/d0cs01575j
6. Ribeiro BD, Coelho MAZ, de Castro AM. Principles of Green Chemistry and White Biotechnology. White Biotechnology for Sustainable Chemistry. 2016; Available from: https://doi.org/10.1039/9781782624080-00001
7. Ding S. Advances in Biocatalysis for Sustainable Pharmaceutical Synthesis: Applications, Technological Progress, and Future Directions. Highlights in Science, Engineering and Technology. 2024; 116 Available from: https://doi.org/10.54097/ehmhaf10
8. Bell EL, Finnigan W, France SP, Green AP, Hayes MA, Hepworth LJ, et al. Biocatalysis. Nature Reviews Methods Primers. 2021; 1 (1). Available from: https://doi.org/10.1038/s43586-021-00044-z
9. Lou WY, Fernández-Lucas J, Ge J, Wu C. Editorial: Enzyme or Whole Cell Immobilization for Efficient Biocatalysis: Focusing on Novel Supporting Platforms and Immobilization Techniques. Frontiers in Bioengineering and Biotechnology. 2021; 9 Available from: https://doi.org/10.3389/fbioe.2021.620292
10. Porto de Souza Vandenberghe L, Karp SG, Binder Pagnoncelli MG, von Linsingen Tavares M, Libardi Junior N, Valladares Diestra K, et al. Classification of enzymes and catalytic properties. Biomass, Biofuels, Biochemicals. 2020; Available from: https://doi.org/10.1016/b978-0-12-819820-9.00002-8
11. Onagun Q, Gbenga AA. Green chemistry in medicinal chemistry: A review on sustainable approaches to the synthesis of biologically active compounds. World Journal of Advanced Research and Reviews. 2024; 24 (2). Available from: https://doi.org/10.30574/wjarr.2024.24.2.3417
12. François JM. How White Biotechnology Can Contribute to Bioeconomy?. Ecological Engineering and Environment Protection. 2022; 2022 (2/2022). Available from: https://doi.org/10.32006/eeep.2022.2.0517
13. O’Connell A, Barry A, Burke AJ, Hutton AE, Bell EL, Green AP, et al. Biocatalysis: landmark discoveries and applications in chemical synthesis. Chemical Society Reviews. 2024; 53 (6). Available from: https://doi.org/10.1039/d3cs00689a
14. Wu S, Snajdrova R, Moore JC, Baldenius K, Bornscheuer UT. Biocatalysis: Enzymatic Synthesis for Industrial Applications. Angewandte Chemie International Edition. 2021; 60 (1). Available from: https://doi.org/10.1002/anie.202006648
15. Simić S, Zukić E, Schmermund L, Faber K, Winkler CK, Kroutil W. Shortening Synthetic Routes to Small Molecule Active Pharmaceutical Ingredients Employing Biocatalytic Methods. Chemical Reviews. 2022; 122 (1). Available from: https://doi.org/10.1021/acs.chemrev.1c00574
16. Olivencia SB, Sasangohar F. Investigating the Food and Drug Administration Biotherapeutics Review and Approval Process: Narrative Review (Preprint). Formative Research. JMIR Publications Inc. 2021; 5 Available from: https://doi.org/10.2196/preprints.14563
17. Cornely OA, Dupont H, Mikulska M, Rautemaa-Richardson R, Garcia-Vidal C, Thompson GR, et al. Rezafungin in special populations with candidaemia and/or invasive candidiasis. Journal of Infection. 2025; 90 (3). Available from: https://doi.org/10.1016/j.jinf.2025.106435
18. Lin SH, Liu JW, Yen YT, Chen MT, Wang JT, Tu YK, et al. Effectiveness of molnupiravir as early treatment for COVID-19 to prevent mortality and hospitalisation in high-risk adults: A systematic review and meta-analysis of randomised trials and real-world studies involving 1,612,082 patients. Journal of Microbiology, Immunology and Infection. 2025; 58 (5). Available from: https://doi.org/10.1016/j.jmii.2025.03.015
19. George KA, Anding AL, van der Flier A, Tomassy GS, Berger KI, Zhang TY, et al. Pompe disease: Unmet needs and emerging therapies. Molecular Genetics and Metabolism. 2025; 143 (3). Available from: https://doi.org/10.1016/j.ymgme.2024.108590
20. Glaspy J, Daley W, Bondarenko I, Rutty D, Chen J. A Phase III, Randomized, Multi-Center, Open-Label, Fixed Dose, Neulasta Active-Controlled Clinical Trial of F-627, a Novel G-CSF, in Women with Breast Cancer Receiving Myelotoxic Chemotherapy. Blood. 2021; 138 (Supplement 1). Available from: https://doi.org/10.1182/blood-2021-145760
21. Jun-ichi N, Soubret A, Buatois S, Charoin JE, Sreckovic S, Bucher C, et al. An Optimized Crovalimab Dose and Regimen Reduced the Formation of Drug-Target-Drug Complexes in Patients with Paroxysmal Nocturnal Hemoglobinuria from the Phase I/II COMPOSER Trial. Blood. 2020; 136 (Supplement 1). Available from: https://doi.org/10.1182/blood-2020-136265
22. Shimozaki K, Ooki A, Yamahata Y, Aoyama T, Yoshino K, Tamba M, et al. Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice. ESMO Gastrointestinal Oncology. 2025; 7 Available from: https://doi.org/10.1016/j.esmogo.2024.100128
23. Cauvin A, Brady K, Cavagnaro J, Luetjens CM. Evaluation of the effect of rozanolixizumab on pregnancy outcomes and pre- and postnatal development in cynomolgus monkeys. Reproductive Toxicology. 2025; 132 Available from: https://doi.org/10.1016/j.reprotox.2024.108823
24. Picavia RM, DeSimone J, Jang S, Stahl C. Treating locally advanced and metastatic cutaneous squamous cell carcinoma with anti-PD-1 drugs: Real-world experience in 72 patients. JAAD International. 2024; 14 Available from: https://doi.org/10.1016/j.jdin.2023.06.013
25. Idris OA, Westgate D, Saadaie Jahromi B, Shebrain A, Zhang T, Ashour HM. PD-L1 Inhibitor Cosibelimab for Cutaneous Squamous Cell Carcinoma: Comprehensive Evaluation of Efficacy, Mechanism, and Clinical Trial Insights. Biomedicines. 2025; 13 (4). Available from: https://doi.org/10.3390/biomedicines13040889
26. Al-Salama ZT. Durvalumab: A Review in Extensive-Stage SCLC. Targeted Oncology. 2021; 16 (6). Available from: https://doi.org/10.1007/s11523-021-00843-0
27. Abdelraheem EMM, Busch H, Hanefeld U, Tonin F. Biocatalysis explained: from pharmaceutical to bulk chemical production. Reaction Chemistry & Engineering. 2019; 4 (11). Available from: https://doi.org/10.1039/c9re00301k
28. Samsonowicz-Górski J, Koszelewski D, Kowalczyk P, Śmigielski P, Hrunyk A, Kramkowski K, et al. Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates. International Journal of Molecular Sciences. 2022; 23 (15). Available from: https://doi.org/10.3390/ijms23158819
29. Wang H, Ma X, Sun L, Bi T, Yang W. Applications of innovative synthetic strategies in anticancer drug discovery: The driving force of new chemical reactions. Bioorganic & Medicinal Chemistry Letters. 2025; 119 Available from: https://doi.org/10.1016/j.bmcl.2025.130096
30. Sengupta S, Das P, Sharma S, Shukla MK, Kumar R, Kumar Tonk R, et al. Role and Application of Biocatalysts in Cancer Drug Discovery. Catalysts. 2023; 13 (2). Available from: https://doi.org/10.3390/catal13020250
31. Imantay A, Mashurov N, Zhaisanbayeva BA, Mun EA. Doxorubicin – Conjugated Nanoparticles for Potential Use as Drug Delivery Systems. Nanomaterials. Multidisciplinary Digital Publishing Institute. 2025; 15 Available from: https://doi.org/10.20944/preprints202412.0425.v1
32. Ahmadi F, Bahmyari M, Akbarizadeh A, Alipour S. Doxorubicin-verapamil dual loaded PLGA nanoparticles for overcoming P-glycoprotein mediated resistance in cancer: Effect of verapamil concentration. Journal of Drug Delivery Science and Technology. 2019; 53 Available from: https://doi.org/10.1016/j.jddst.2019.101206
33. Wilson NR, Wiele AJ, Surasi DS, Rao P, Sircar K, Tamboli P, et al. Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma. Clinical Genitourinary Cancer. 2021; 19 (6). Available from: https://doi.org/10.1016/j.clgc.2021.08.007
34. Yang A, Dong X, Bai Y, Sheng S, Zhang Y, Liu T, et al. Doxorubicin/CpG self-assembled nanoparticles prodrug and dendritic cells co-laden hydrogel for cancer chemo-assisted immunotherapy. Chemical Engineering Journal. 2021; 416 Available from: https://doi.org/10.1016/j.cej.2021.129192
35. Pușcașu C, Negreș S, Zbârcea CE, Chiriță C. Unlocking New Therapeutic Options for Vincristine-Induced Neuropathic Pain: The Impact of Preclinical Research. Life. 2024; 14 (11). Available from: https://doi.org/10.3390/life14111500
36. Dunn PJ, Wells AS, Williams MT. Green Chemistry in the Pharmaceutical Industry. Wiley. 2010; Available from: https://doi.org/10.1002/9783527629688
37. Huang X, Cao M, Zhao H. Integrating biocatalysis with chemocatalysis for selective transformations. Current Opinion in Chemical Biology. 2020; 55 Available from: https://doi.org/10.1016/j.cbpa.2020.02.004
38. Clayton AD, Labes R, Blacker AJ. Combination of chemocatalysis and biocatalysis in flow. Current Opinion in Green and Sustainable Chemistry. 2020; 26 Available from: https://doi.org/10.1016/j.cogsc.2020.100378
39. Goodwin NC, Morrison JP, Fuerst DE, Hadi T. Biocatalysis in Medicinal Chemistry: Challenges to Access and Drivers for Adoption. ACS Medicinal Chemistry Letters. 2019; 10 (10). Available from: https://doi.org/10.1021/acsmedchemlett.9b00410
40. Madden KS, Todd PMT, Urata K, Russell AJ, Vincent KA, Reeve HA. A pharmacophore-based approach to demonstrating the scope of alcohol dehydrogenases. Bioorganic & Medicinal Chemistry. 2023; Available from: https://doi.org/10.26434/chemrxiv.13134767.v1
41. Chakrabarty S, Romero EO, Pyser JB, Yazarians JA, Narayan ARH. Chemoenzymatic Total Synthesis of Natural Products. Accounts of Chemical Research. 2021; 54 (6). Available from: https://doi.org/10.1021/acs.accounts.0c00810
42. Zhang Q, Wu ZM, Liu S, Tang XL, Zheng RC, Zheng YG. Efficient Chemoenzymatic Synthesis of Optically Active Pregabalin from Racemic Isobutylsuccinonitrile. Organic Process Research & Development. 2019; 23 (9). Available from: https://doi.org/10.1021/acs.oprd.9b00285
43. Tanifuji R, Oguri H. Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations. Beilstein Journal of Organic Chemistry. 2024; 20 Available from: https://doi.org/10.3762/bjoc.20.151
44. Kinner A, Nerke P, Siedentop R, Steinmetz T, Classen T, Rosenthal K, et al. Recent Advances in Biocatalysis for Drug Synthesis. Biomedicines. 2022; 10 (5). Available from: https://doi.org/10.3390/biomedicines10050964
45. Rosing J. Influence of Protein Engineering in Biotechnology and Medicine. Transcriptomics: Open Access. 2023; 9 (1). Available from: https://doi.org/10.35248/2329-8936.23.9.140
46. Mao S, Jiang J, Xiong K, Chen Y, Yao Y, Liu L, et al. Enzyme Engineering: Performance Optimization, Novel Sources, and Applications in the Food Industry. Foods. 2024; 13 (23). Available from: https://doi.org/10.3390/foods13233846
47. Victorino da Silva Amatto I, Gonsales da Rosa-Garzon N, Antônio de Oliveira Simões F, Santiago F, Pereira da Silva Leite N, Raspante Martins J, et al. Enzyme engineering and its industrial applications. Biotechnology and Applied Biochemistry. 2022; 69 (2). Available from: https://doi.org/10.1002/bab.2117
48. Heckmann CM, Paradisi F. Looking Back: A Short History of the Discovery of Enzymes and How They Became Powerful Chemical Tools. ChemCatChem. 2020; 12 (24). Available from: https://doi.org/10.1002/cctc.202001107
49. Bell EL, Finnigan W, France SP, Green AP, Hayes MA, Hepworth LJ, et al. Biocatalysis. Nature Reviews Methods Primers. 2021; 1 (1). Available from: https://doi.org/10.1038/s43586-021-00044-z
50. Bansal S, Kundu B. Protein engineering: Methods and applications. Advances in Protein Molecular and Structural Biology Methods. 2022; Available from: https://doi.org/10.1016/b978-0-323-90264-9.00039-8
51. Farhan A. Biotransformation of Anti-cancer Drugs: Role of Cytochrome P450 Enzymes. International Journal Of Pharmaceutical, Chemical And Biological Sciences. 2024, 14(3), 01-02
52. Zhang X, Luo W, Yao Y, Luo X, Han C, Zhong Y, et al. Enhanced chemoselectivity of a plant cytochrome P450 through protein engineering of surface and catalytic residues. aBIOTECH. 2021; 2 (3). Available from: https://doi.org/10.1007/s42994-021-00056-z
53. Paul C, Hanefeld U, Hollmann F, Qu G, Yuan B, Sun Z. Enzyme engineering for biocatalysis. Molecular Catalysis. 2024; 555 Available from: https://doi.org/10.1016/j.mcat.2024.113874
54. Carrera-Pacheco SE, Mueller A, Puente-Pineda JA, Zúñiga-Miranda J, Guamán LP. Designing cytochrome P450 enzymes for use in cancer gene therapy. Frontiers in Bioengineering and Biotechnology. 2024; 12 Available from: https://doi.org/10.3389/fbioe.2024.1405466
55. Bassani D, Moro S. Past, Present, and Future Perspectives on Computer-Aided Drug Design Methodologies. Molecules. 2023; 28 (9). Available from: https://doi.org/10.3390/molecules28093906
56. Markus B, Christian C G, Andreas K, Arkadij K, Stefan L, Gustav O, et al. Accelerating Biocatalysis Discovery with Machine Learning: A Paradigm Shift in Enzyme Engineering, Discovery, and Design. ACS Catalysis. 2023; 13 (21). Available from: https://doi.org/10.1021/acscatal.3c03417
57. Liu K, Sun Y, Cao M, Wang J, Lu JR, Xu H. Rational design, properties, and applications of biosurfactants: a short review of recent advances. Current Opinion in Colloid & Interface Science. 2020; 45 Available from: https://doi.org/10.1016/j.cocis.2019.12.005
58. Song Z, Zhang Q, Wu W, Pu Z, Yu H. Rational design of enzyme activity and enantioselectivity. Frontiers in Bioengineering and Biotechnology. 2023; 11 Available from: https://doi.org/10.3389/fbioe.2023.1129149
59. Zhou L, Tao C, Shen X, Sun X, Wang J, Yuan Q. Unlocking the potential of enzyme engineering via rational computational design strategies. Biotechnology Advances. 2024; 73 Available from: https://doi.org/10.1016/j.biotechadv.2024.108376
60. Zhang Y, Luo M, Wu P, Wu S, Lee TY, Bai C. Application of Computational Biology and Artificial Intelligence in Drug Design. International Journal of Molecular Sciences. 2022; 23 (21). Available from: https://doi.org/10.3390/ijms232113568
61. Derat E, Kamerlin SCL. Computational Advances in Protein Engineering and Enzyme Design. The Journal of Physical Chemistry B. 2022; 126 (13). Available from: https://doi.org/10.1021/acs.jpcb.2c01198
62. Shurtleff VW, Layton ME, Parish CA, Perkins JJ, Schreier JD, Wang Y, et al. Invention of MK-7845, a SARS-CoV2 3CL Protease Inhibitor Employing a Novel Difluorinated Glutamine Mimic. Journal of Medicinal Chemistry. 2024; 67 (5). Available from: https://doi.org/10.1021/acs.jmedchem.3c02248.s002
63. Sangha R, Kuruvilla J, Sehn LH, Weickert M, Beauchamp E, Gamma JM, et al. Zelenirstat Nmt Inhibitor in Patients with Relapsed/Refractory B-Cell Lymphoma and Acute Myelogenous Leukemia: Mechanistic Insights and Clinical Outcomes. Blood. 2024; 144 (Supplement 1). Available from: https://doi.org/10.1182/blood-2024-208480
64. Gupta A, Parveen D, Azam F, Shaquiquzzaman M, Akhter M, Jaremko M, et al. Mechanistic insights into novel cyano-pyrimidine pendant chalcone derivatives as LSD1 inhibitors by docking, ADMET, MM/GBSA, and molecular dynamics simulation. Biochemistry and Biophysics Reports. 2025; 41 Available from: https://doi.org/10.1016/j.bbrep.2025.101937
65. Wang Y, Xue P, Cao M, Yu T, Lane ST, Zhao H. Directed Evolution: Methodologies and Applications. Chemical Reviews. 2021; 121 (20). Available from: https://doi.org/10.1021/acs.chemrev.1c00260
66. Sellés Vidal L, Isalan M, Heap JT, Ledesma-Amaro R. A primer to directed evolution: current methodologies and future directions. RSC Chemical Biology. 2023; 4 (4). Available from: https://doi.org/10.1039/d2cb00231k
67. Fan S, Lü X, Wei X, Lü R, Feng C, Jin Y, et al. Computational design of α-amylase from Bacillus licheniformis to increase its activity and stability at high temperatures. Computational and Structural Biotechnology Journal. 2024; 23 Available from: https://doi.org/10.1016/j.csbj.2024.02.005
68. Yin Q, Xiang L, Han X, Zhang Y, Lyn R, Yuan L, et al. The evolutionary advantage of artemisinin production by Artemisia annua. Trends in Plant Science. 2025; 30 (2). Available from: https://doi.org/10.1016/j.tplants.2024.09.006
69. Xue C, Zhang M, Yao R. Gapless biosynthetic pathway enables sustainable paclitaxel production. Trends in Plant Science. 2024; 29 (9). Available from: https://doi.org/10.1016/j.tplants.2024.05.005
70. Wang Y, Subrizi F, Carter EM, Sheppard TD, Ward JM, Hailes HC. Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants. Nature Communications. 2022; 13 (1). Available from: https://doi.org/10.1038/s41467-022-33122-1
71. Xiong W, Liu B, Shen Y, Jing K, Savage TR. Protein engineering design from directed evolution to de novo synthesis. Biochemical Engineering Journal. 2021; 174 Available from: https://doi.org/10.1016/j.bej.2021.108096
72. Goverde CA, Wolf B, Khakzad H, Rosset S, Correia BE. De novo protein design by inversion of the AlphaFold structure prediction network. Protein Science. 2023; 32 (6). Available from: https://doi.org/10.1101/2022.12.13.520346
73. Cummins MC, Tripathy A, Sondek J, Kuhlman B. De novo design of stable proteins that efficaciously inhibit oncogenic G proteins. bioRxiv. 2023; Available from: https://doi.org/10.1101/2023.03.28.534629
74. Mirsalami SM, Mirsalami M, Ghodousian A. Techniques for immobilizing enzymes to create durable and effective biocatalysts. Results in Chemistry. 2024; 7 Available from: https://doi.org/10.1016/j.rechem.2024.101486
75. Cutlan R, De Rose S, Isupov MN, Littlechild JA, Harmer NJ. Using enzyme cascades in biocatalysis: Highlight on transaminases and carboxylic acid reductases. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2020; 1868 (2). Available from: https://doi.org/10.1016/j.bbapap.2019.140322
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