Crystal structure and catalytic mechanism of drimenol synthase, an unusual bifunctional terpene cyclase-phosphatase.

ABSTRACT: Drimenol synthase from Aquimarina spongiae (AsDMS) is a highly unusual chimera 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. The AsDMS structure exhibits a didomain architecture consisting of a terpene cyclase β domain and a haloacid dehalogenase-like phosphatase domain, with two distinct active sites located on opposite sides of the protein. Mechanistic studies show that dephosphory

SUBMITTER: Osika KR 

PROVIDER: S-EPMC12232559 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature