Unlocking hidden treasures: the evolution of high-throughput mass spectrometry in screening for cryptic natural products

Covering: 1994 to 2024 Historically, microbial natural product discovery has been predominantly guided by biological activity from crude microbial extracts with metabolite characterization proceeding one molecule at a time. Despite decades of bioactivity-guided isolations, genomic evidence now suggests that we have only accessed a small fraction of the total natural product potential from microorganisms and that the products of the vast majority of biosynthetic pathways remain to be identified. Here we describe recent advancements that have enabled high-throughput mass spectrometry and comparative metabolomics, which in turn facilitate high-throughput natural product discovery. These advancement promise to fully unlock the reservoir of microbial natural products.