(228p) Discovery and Characterization of Novel Plant Natural Products through Biosynthetic Clusters
Plant natural products (PNPs) have been a rich source for discovery of pharmaceutical and antimicrobial compounds. While the onset of next-generation sequencing has dramatically increased the number of sequenced genomes, providing an invaluable resource for pathway discovery of natural products, the number of new natural product-derived or -inspired drugs per year has remained approximately constant over the past 34 years (Newman et al). In order to help close the gap between availability of genomic information and discovery of novel PNPs, herein we have developed a high-throughput platform for discovery of PNPs by exploiting the genomic clustering of biosynthetic genes. Though biosynthetic clustering is a common phenomenon in bacteria, until recently it has been largely overlooked in plants; however, with growing interest for new ways to discover novel PNPs, more and more biosynthetic clusters have been shown in plants (Nützmann et al). Through genomic mining and transcriptomic co-expression analysis, our platform assembles and filters potential clusters to a small list of top candidates. These candidates are then combinatorially tested for new PNPs in a plant transient expression system using untargeted metabolomics. Our platform combines rapid computational and experimental processes for the assembly, filtering, and characterization of potential biosynthetic clusters to the end of PNP discovery.
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 79, 629-661 (2016).
Nützmann, H.W.; Osbourn, A. Gene clustering in plant specialized metabolism. Curr. Opin. Biotechnol. 26, 91-99 (2014).