Genome Mining of Bacterial Cytochrome P450 Enzymes for Novel Biocatalysts

Caitlin A. McCadden, Tyler Alsup, Zining Li, Baofu Xu, Jeffrey Rudolf

University of Florida

Biocatalysis employs both in vitro enzymes and whole-cell methods to provide enzymatic approaches to synthesizing complex active ingredients, key intermediates, and derivatizing analogs. Using a genome mining approach, we initiated an in vivo screen to probe the biocatalytic functionality of predicted cytochrome P450 genes from Streptomyces. In doing so, we elucidated the structures of several functionalized products. Most notable is the conversion of abietic acid to 15-hydroxydehydroabietic acid which involves both dehydrogenation and hydroxylation reactions. Hydroxylation is one the most common P450-catalyzed reactions while dehydrogenation is comparatively less explored, especially in biosynthetic and mechanistic terms.