Structure-Based Engineering of a Sesquiterpene Cyclase to Generate an Alcohol Product: Conversion of <i>epi</i>-Isozizaene Synthase into α-Bisabolol Synthase.

ABSTRACT: The sesquiterpene cyclase epi-isozizaene synthase (EIZS) from Streptomyces coelicolor catalyzes the metal-dependent conversion of farnesyl diphosphate (FPP) into the complex tricyclic product epi-isozizaene. This remarkable transformation is governed by an active site contour that serves as a template for catalysis, directing the conformations of multiple carbocation intermediates leading to the final product. Mutagenesis of residues defining the active site contour remolds its three-dimensional shape and reprograms the cyclization cascade to generate alternative cyclization products. In some cases, mutagenesis enables alternative chemistry to quench carbocation intermediates, e.g., through hydroxylation. Here, we combine structural and biochemical data from previously

SUBMITTER: Eaton SA 

PROVIDER: S-EPMC10961106 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature