Research

       The Manley Lab is interested in the enzymology underlying the biosynthesis of natural products. Natural products exhibit unusual chemical structures that confer their potent bioactivities, including antimicrobial activity, nutrient sequestration, signaling, and more. To achieve the complex and challenging chemical transformations in natural product chemistry, nature often employs metal ions as enzymatic cofactors, which are capable of leveraging the oxidizing power of molecular oxygen as a cosubstrate to catalyze such reactions. Bacterial genomes encode numerous uncharacterized metalloenzymes, representing untapped chemical diversity in nature. The goal of our lab is to use genome mining to uncover new biosynthetic gene clusters containing metalloenzymes and to reveal the natural products that they produce. We also explore the bioactivities of the new natural products. Additionally, we investigate the mechanisms by which these metalloenzymes activate oxygen to achieve their biosynthetic function, aiming to tap into the bioengineering potential of such enzymes.