Exploiting Microbiome and Synthetic Biology to Discover and Produce Naturally Occurring Antibiotics

In this proposal, we aim to validate the human gut microbiome and arid soil as a source of antibiotic natural products (NPs ) by using ametagenomic NP discovery platform developed at Radiant Genomics. Recent studies suggest that the genomes of uncultivated microorganisms,like their cultivated counterparts, encode an enormous number of NPs. Gaining systematic access to NPs using standard, cultivation-dependentapproaches, however, remains challenging as 10^7 clones/day. Because our libraries are renewably cloned, we can rapidly isolate,assemble, refactor and heterologously express selected gene clusters in our panel of metabolically-optimized, gram(+ and -) industrial hoststrains, resulting in high-throughput, systematic identification of novel NPs.