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.

The environmental impacts of the postindustrial era, which rely on fossil fuels, have compelled a reconsideration of the future of energy and chemical industries. Fungi are a valuable resource for improving a circular economy through the enhanced valorization of biomass and plant waste. They harbor a great diversity of oxidative enzymes, especially in their secretome. Enzymatic breakdown of the plant cell wall complex and lignocellulosic biomass yields sugars for fermentation and biofuel production, as well as aromatic compounds from lignin that can serve as raw materials for the chemical industry. To harness the biocatalytic potential, it is essential to identify and explore wild-type fungi and their secretomes. This study successfully combined genome mining and activity screening to uncover the oxidative potential of a collection of underexploited ascomycetes and basidiomycetes. The heme peroxidase and laccase activities of four promising candidates, Bipolaris victoriae, Colletotrichum sublineola, Neofusicoccum parvum and Moesziomyces antarcticus, were investigated to gain a deeper insight into their enzyme secretion. Furthermore, a plant-based medium screening with the phytopathogen C. sublineola revealed that soybean meal is a beneficial component to trigger the production and secretion of enzymes that catalyze H₂O₂-dependent oxidations. These results demonstrate that understanding fungal secretomes and their enzymatic potential opens exciting avenues for sustainable biotechnological applications across various industries.