Biocatalysis in Therapeutic Development: From Mechanism to Manufacturing

Biocatalysis is an increasingly important approach in therapeutic discovery and pharmaceutical manufacturing, enabling selective and efficient transformations under mild reaction conditions. Enzymes can provide access to complex therapeutic molecules and valuable intermediates that may be challenging to prepare through conventional chemical synthesis, while potentially reducing waste, energy consumption, and the use of hazardous reagents. However, translating biocatalytic transformations from academic proof-of-concept studies into reliable, scalable, and economically viable manufacturing processes remains challenging. Important questions concern how enzyme structure and mechanism determine catalytic performance, how biocatalysts can be engineered for practical applications, and how laboratory-scale reactions can be integrated into robust production processes. Recent advances in protein engineering, directed evolution, computational design, high-throughput screening, and process intensification are expanding the range of viable biocatalytic reactions. Nevertheless, further work is needed to connect mechanistic understanding and catalyst development with substrate availability, reaction engineering, downstream processing, regulatory requirements, and scale-up.This Research Topic aims to advance understanding and application of biocatalysis across the therapeutic development pipeline, from enzyme mechanism and biocatalyst discovery to the synthesis, optimization, and manufacturing of therapeutic compounds. It will bring together academic and industrial perspectives to examine how enzymes can enable new synthetic strategies, improve the preparation of active pharmaceutical ingredients and drug intermediates, and support more efficient and sustainable production. Contributions may address mechanistic questions, test hypotheses concerning enzyme activity or selectivity, demonstrate proof-of-concept transformations, or report the development and scale-up of processes with practical manufacturing relevance.To gather further insights into biocatalytic approaches for therapeutic discovery and manufacturing, this Research Topic will cover studies ranging from fundamental enzyme chemistry and catalyst development to process implementation and scale-up. Submissions should maintain a clear connection between enzyme chemistry and biological or therapeutic applications, while claims concerning industrial relevance should be supported by appropriate experimental or process data. We welcome articles addressing, but not limited to, the following themes:- Mechanistic and structural studies of enzymes relevant to therapeutic synthesis- Discovery, screening, characterization, and optimization of biocatalysts- Enzyme engineering, directed evolution, and strategies to improve activity, selectivity, stability, or substrate scope- Biocatalytic routes to active pharmaceutical ingredients and drug intermediates- Chemoenzymatic synthesis and integration of biocatalysis with conventional chemical methods- Computational, machine-learning, and data-driven approaches to biocatalyst design- Reaction engineering and process development informed by enzyme structure–function relationships, and scale-up of biocatalytic transformations- Whole-cell, cell-free, immobilized-enzyme, and continuous biocatalytic systems- Optimization of reaction conditions, cofactor regeneration, and enzyme reuse- Downstream processing and process intensification as shaped by catalyst chemistry, with sustainability and life-cycle considerations- Academic proof-of-concept studies and industrial case studies where enzyme chemistry drives the manufacturing outcome Topic editors: Noah Dunham, Sebastian Cosgrove, Yang Hai, Scott France Source: https://www.frontiersin.org/research-topics/85692/biocatalysis-in-therapeutic-development-from-mechanism-to-manufacturing