Bacteria and fungi offer many new compounds yet to be discovered and exploited as leads in 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 modern mass spectrometry with accurate mass, two new and scalable approaches to identification of natural products and their biosynthetic gene clusters have been developed. For actinobacteria, the technique of “metabologenomics” has been reported and led to discovery of compounds like tambromycin, which harbors a new amino acid and antiproliferative activity (ACS Central Sci. 2016, 2(2):99-108.). This talk will also focus on a new platform for fungi, a platform called “FAC-MS”. Using FAC-MS we uncovered 15 new systems (majority were cryptic) across three fungal species, including valactamide - a hybrid molecule made by a new PKS/NRPS biosynthetic gene cluster (cf. Clevenger et al., cover article in August, 2017 issue of Nat. Chem. Biol.: 13 (8), 895-901). We seek to leverage these interpreted genomes, new tools and their data clouds to deliver renewable, reliable sources for the discovery of new natural products. Our aim is 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 in of high-throughput natural products discovery.

Two scalable platforms for large scale discovery of microbial natural products

2019 Fall National Meeting

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