Mechanistic Characterization of a Multiproduct Sesquiterpene Synthase for Triquinanes and Quadranes from Streptomyces pathocidini

Abstract

Through genome mining, a sesquiterpene synthase from Streptomyces pathocidini was discovered and shown to generate a mixture of multiple products. Isotopic labeling experiments and DFT calculations were performed for detailed insight into its complex cyclization mechanism. Enzyme engineering through site-directed mutagenesis gave access to four additional products, one of which occurred as a minor constituent in the wild-type enzyme.