Crystal Structure and Catalytic Mechanism of Drimenol Synthase, a Bifunctional Terpene Cyclase-Phosphatase.

ABSTRACT: Drimenol synthase from Aquimarina spongiae (AsDMS) is a highly unusual bifunctional sesquiterpene synthase that integrates two distinct, sequential isoprenoid processing activities within a single polypeptide chain. AsDMS catalyzes the class II cyclization of farnesyl diphosphate (FPP) to form drimenyl diphosphate, which then undergoes enzyme-catalyzed hydrolysis to yield drimenol, a bioactive sesquiterpene alcohol with antifungal and anticancer properties. Here, we report the X-ray crystal structures of AsDMS and its complex with a sesquiterpene thiol, which are the first of a terpene cyclase-phosphatase. The AsDMS structure exhibits a two-domain architecture consisting of a terpene cyclase β domain and a haloacid dehalogenase (HAD)-like phosphatase domain, with two distinct active

SUBMITTER: Osika KR 

PROVIDER: S-EPMC11844523 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature