Microbial genomics: New opportunities for natural product biosynthesis, engineering, and drug discovery

Natural products are among the best sources of drugs and drug leads and serve as outstanding small molecule probes for dissecting fundamental biological processes. Natural product biosynthesis continues to push the frontier of modern chemistry, biochemistry, and molecular biology by revealing novel chemical reactions, complex enzyme systems, and intricate regulatory mechanisms. The progress made in the last two decades in connecting natural products to the genes that encode their biosynthesis has fundamentally changed the landscape of natural products research and sparked the emergence of a suite of contemporary approaches to natural products discovery. Genetic manipulation of natural product biosynthetic machineries offers a promising alternative to generate natural product structural diversity. Selected examples from our current research will be presented to highlight the opportunities for natural product biosynthesis, engineering, and drug discovery.