Recent Advances in Biocatalysis for Drug Synthesis

Abstract

Biocatalysis is constantly providing novel options for the synthesis of active pharmaceutical ingredients (APIs). In addition to drug development and manufacturing, biocatalysis also plays a role in drug discovery and can support many active ingredient syntheses at an early stage to build up entire scaffolds in a targeted and preparative manner. Recent progress in recruiting new enzymes by genome mining and screening or adapting their substrate, as well as product scope, by protein engineering has made biocatalysts a competitive tool applied in academic and industrial spheres. This is especially true for the advances in the field of nonribosomal peptide synthesis and enzyme cascades that are expanding the capabilities for the discovery and synthesis of new bioactive compounds via biotransformation. Here we highlight some of the most recent developments to add to the portfolio of biocatalysis with special relevance for the synthesis and late-stage functionalization of APIs, in order to bypass pure chemical processes.

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

“…Finally, although microbial lipases could be considered one of the most versatile, they alone can hardly reach the ideal goal of a predominant enzyme synthesis of an API, especially if they involve redox steps; thus, it is necessary to explore the development of enzyme cascades which include the aspects previously listed [ 236 , 237 , 238 , 239 ]. Indeed, the implementation of enzyme cascades in the synthesis of APIs with possibilities of industrial exploitation were recently reviewed [ 240 ].…”

Opportunities for Accelerating Drug Discovery and Development by Using Engineered Drug-Metabolizing Enzymes

“…Using enzymes offers advantages of greater selectivity in the site of modification, since the topography of the enzyme's active site directs the modification to specific sites and faces of the molecule (e.g., (Le-Huu et al, 2016)). Moreover, biocatalysis shortens synthetic routes (Simić et al, 2022), can be done under mild conditions and reduces the reliance on solvents and other toxic chemicals (Kinner et al, 2022).…”

The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

“…This perspective specifically aims to focus on recent key examples of implementation of biocatalysis for scalable syntheses of pharmaceutical intermediates. Several excellent reviews have been published on industrial biocatalysis covering various aspects of enzymatic transformations for drug development. ,,− As such, this perspective does not aim to be comprehensive but rather highlight the current state-of-the-art of preparative enzymatic synthesis in an industrial setting. Therefore, the use of biocatalysis for small-scale pharmaceutical metabolite synthesis, lead diversification, ,,, bioconjugation, and selective protein modification − will not be focused upon in this article.…”