Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds
Lindsay K. Caesar, Matthew T. Robey, Michael Swyers, Md. Nurul Islam, Rosa Ye, Purav P. Vagadia, Gary E. Schiltz, Paul M. Thomas, Chengcang Wu, Neil L. Kelleher, Nancy P. Keller, Jin Woo Bok
Abstract
encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies fungi employ for diversifying and protecting themselves against secondary metabolites. The observations in this study set the stage for further in-depth studies into the function of duplicated IDOs present in fungal biosynthetic gene clusters and presents a strategy for accessing the biosynthetic potential of gene clusters containing duplicated primary metabolic genes.