Integrated Metabolomic-Genomic Workflows Accelerate Microbial Natural Product Discovery

Abstract

The pairing of analytical chemistry with genomic techniques represents a new wave in natural product chemistry. With an increase in the availability of sequencing and assembly of microbial genomes, interrogation into the biosynthetic capability of producers with valuable secondary metabolites is possible. However, without the development of robust, accessible, and medium to high throughput tools, the bottleneck in pairing metabolic potential and compound isolation will continue. Several innovative approaches have proven useful in the nascent stages of microbial genome-informed drug discovery. Here, we consider a number of these approaches which have led to prioritization of strain targets and have mitigated rediscovery rates. Likewise, we discuss integration of principles of comparative evolutionary studies and retrobiosynthetic predictions to better understand biosynthetic mechanistic details and link genome sequence to structure. Lastly, we discuss advances in engineering, chemistry, and molecular networking and other computational approaches that are accelerating progress in the field of omic-informed natural product drug discovery. Together, these strategies enhance the synergy between cutting edge omics, chemical characterization, and computational technologies that pitch the discovery of natural products with pharmaceutical and other potential applications to the crest of the wave where progress is ripe for rapid advances.