Support is requested for a Keystone Symposia conference entitled Natural Products and Synthetic Biology: Parts and Pathways, organized by Drs. Jon C. Clardy, Yi Tang and Sean F. Brady. The conference will be held January 21 - 24, 2018 in Olympic Valley, California. Natural products, the structurally diverse family of small molecules produced by living organisms in an idiosyncratic fashion, have provided the basis for the majority of our therapeutic agents used to treat infectious diseases, cancer and immune disorders. Whole genome sequencing of producing organisms, especially bacteria and fungi, reveals that we have discovered only a fraction of these biosynthetically derived small molecules; a substantial fraction of natural product chemical space still represents ?dark matter? (i.e., molecules predicted by bioinformatics analysis that have yet to be observed experimentally). Diversity springs from variations in genetically encoded biosynthetic enzymes, environmental stimuli that regulate expression of these genes and the inherent combinatorial expansion resulting from multi-enzyme biosynthetic pathways. Closing this gap between our current inventory and the genomic potential has become an important goal for basic and applied science; synthetic biology coupled with bioinformatic analysis has become the primary research tool for this effort. Bioinformatic mining continues to reveal the enzymes and pathways that nature uses, and synthetic biology has begun to reassemble or refactor these pathways to produce known and unknown products in new hosts. This conference brings together researchers in fields ranging from microbiology to botany, bioinformatics, gene synthesis and assembly, covering the spectrum from basic to industrial applications.
Natural products have provided the basis for the majority of our therapeutic agents used to treat infectious diseases, cancer and immune disorders. Whole genome sequencing and bioinformatics analysis indicates a substantial untapped reservoir of ?dark matter? of natural products (i.e., molecules predicted by bioinformatic analysis that never show up in a laboratory setting). By closing the gap between our current inventory and the genomic potential of this ?dark matter?, basic and applied science can discover new therapeutic agents to treat human diseases.
