Living systems produce a tremendous diversity of small molecules that have transformed society. These natural products serve as the basis for a wide array of chemical functions from drugs and pesticides to food preservatives and materials. Interestingly, although tens of thousands of natural products have been characterized to date, genome sequencing efforts of the past decade have revealed that the known set of natural products represents only about ten percent of all natural products that exist. Our group is addressing the fundamental challenge of accelerating the rate of discovery and characterization of novel natural products and natural product-like compounds. To do so, we are using the tools of genome mining, synthetic biology, directed evolution, and next generation sequencing. Our goal is to help address societal challenges such as the spread of antibiotic resistant bacteria through understanding and engineering natural product biosynthesis.