Applications of machine learning in microbial natural product drug discovery

INTRODUCTION: Natural products (NPs) are a desirable source of new therapeutics due to their structural diversity and evolutionarily optimized bioactivities. NPs and their derivatives account for roughly 70% of approved pharmaceuticals. However, the rate at which novel NPs are discovered has decreased. To accelerate the microbial NP discovery process, machine learning (ML) is being applied to numerous areas of NP discovery and development. AREAS COVERED: This review explores the utility of ML at various phases of the microbial NP drug discovery pipeline, discussing concrete examples throughout each major phase: genome mining, dereplication, and biological target prediction. Moreover, the authors discuss how ML approaches can be applied to semi-synthetic approaches to drug discovery. EXPERT OPINION: Despite the important role that microbial NPs play in the development of novel drugs, their discovery has declined due to challenges associated with the conventional discovery process. ML is positioned to overcome these limitations given its ability to model complex datasets and generalize to novel chemical and sequence space. Unsurprisingly, ML comes with its own limitations that must be considered for its successful implementation. The authors stress the importance of continuing to build high quality and open access NP datasets to further increase the utility of ML in NP discovery.