Rewiring natural product drug discovery through synthetic microbiology

Natural product chemicals have historically been discovered based on their structural and biological properties. With the ease and affordability of genome sequencing today, a new era in natural product discovery is unfolding in which genomics and biosynthesis are together fostering new innovations in compound discovery. This orthogonal discovery approach takes advantage of the biosynthetic potential of a genome-sequenced organism to design hypothesis-driven experiments to rapidly find new chemical entities that are desperately needed in the drug discovery and development pipeline. Examples from the author's laboratory will highlight the myriad of available and evolving genome mining approaches to connect orphan biosynthetic genes to new natural product molecules.