Bacteria and fungi offer many new compounds yet to be discovered and exploited as leads in crop protection and drug discovery campaigns. The genomics era has ushered in a wealth of information about the natural product biosynthetic arsenals of both, promising vast new collections of fine chemicals. However, tools to convert that genomic knowledge into the promised wealth of new molecules have only recently produced “big data” and begun to emerge. Leveraging genome sequencing and mass spectrometry-based metabolomics with accurate mass, new and scalable approaches to identification of natural products and their biosynthetic gene clusters have been developed. One of the first was the technique of “metabologenomics” (reported in 2014) and led to discovery of dozens of new compounds like tambromycin, which harbors a new amino acid and antiproliferative activity (ACS Central Sci. 2016, 2(2):99-108.). This platform for “high-throughput discovery” of natural products also identify the biosynthetic gene clusters that encode their production, giving major insights into biosynthesis, structure, mode of action and provide actionable information to overexpress “Nature’s drugs” to high  titers. The talk will also describe an interpreted atlas of &gt;35k gene clusters derived from &gt;1000 fungal genomes (PNAS USA, 2021, in press). Combined with new tools and data clouds, this field is poised to deliver renewable, reliable sources for the discovery of new natural products. We are well en route to regularize and domesticate large swaths of the bacterial and fungal natural products for exploitation in the public and private sectors in the dawning era of “high- throughput” natural products discovery.

Scaling multi-omics to uncover microbial natural products for enhanced sustainability

ACS Fall 2021

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