1,2,3,4,5Department of Neurology, Diponegoro University / Dr. Kariadi Hospital Semarang – Indonesia
1Email: retnaku_icu@yahoo.com. ORCID: 0000-0003-1072-6123
2Email: bariscatur@yahoo.com. ORCID: 0000-0001-8492-2018
3Email: gerardjuswanto@gmail.com. ORCID: 0009-0000-4340-0301
4Email: hayuningtyas.dian@gmail.com. ORCID: 0009-0007-0094-3454
5Ruten Inc. Email: kazutaka@ruten-neuro.com. ORCID: 0000-0001-7679-0430
Received: 12th Dec, 2025; Revised: 12th Feb 2026; Accepted: 13th Feb, 2026; Available Online: 10th March, 2026
Enzyme-catalyzed transformations have emerged as a sustainable and efficient approach in modern medicinal chemistry and drug delivery system, offering high chemo-, regio-, and stereoselectivity under mild and environmentally benign conditions. In contrast to conventional synthetic approaches that often rely on harsh reaction conditions and toxic reagents, biocatalytic processes significantly reduce the environmental impact while improving reaction efficiency and product specificity. Thereby, it aligns closely with the core principles of green chemistry. This paradigm shift is particularly significant in the synthesis of complex, chiral active pharmaceutical ingredients (APIs), where enzymatic precision can substantially reduce reaction steps, waste generation, and overall process costs.
This study highlights the role of enzyme-catalyzed reactions in sustainable drug development, and modification of pharmaceutical ingredients (APIs), with particular emphasis on their application in drug delivery technology. Key enzyme classes—including oxidoreductases, transferases, hydrolases, and lyases are critically examined for their mechanistic contributions to modern synthetic strategies. Advances in protein engineering notably directed evolution and structure-guided design, have further expanded the substrate stability, specificity and scalability for industrial application. Furthermore, the integration of multi-enzyme cascade reactions and chemo-enzymatic pathways has facilitated the efficient synthesis of structurally complex molecules with enhanced efficiency and reduced environmental footprint. The impact of biocatalysis on green chemistry metrics including atom economy, E-factor reduction, and process intensification is evaluated. Selected case studies illustrate the successful implementation of enzymatic strategies in stereoselective synthesis, late-stage functionalization, and green manufacturing of pharmaceuticals.
However, challenges related to enzyme stability, cofactor dependency, and large scale process scalability remains critical considerations. Emerging trends—including the application of artificial intelligence and machine learning in enzyme discovery, optimization, and reaction prediction—are explored as transformative tools for accelerating innovation in this domain. Collectively, enzyme-catalyzed reactions represent a scientifically robust and industrially viable pathway for drug delivery and toward sustainable medicinal chemistry.
Keywords: Biocatalysis; drug delivery system; Sustainable medicinal chemistry; Green synthesis; Active pharmaceutical ingredients(API); Enzyme engineering; Directed evolution; Chemoenzymatic synthesis; Process intensification
How to cite this article: Parveen A, R A, Sunitha P, Pasumarthi B, Nakkella AK. Enzyme-Catalyzed Reactions in Sustainable Medicinal Chemistry. Int J Drug Deliv Technol. 2026;16(3): 418-428. DOI: 10.25258/ijddt.16.3.48
Source of support: Nil.
Conflict of interest: None