A terpene synthase-cytochrome P450 cluster in Dictyostelium discoideum produces a novel trisnorsesquiterpene

Abstract

Terpenoids are enormously diverse, but our knowledge of their biosynthesis and functions is limited. Here we report on a terpene synthase (<i>DdTPS8</i>)-cytochrome P450 (<i>CYP521A1</i>) gene cluster that produces a novel C12 trisnorsesquiterpene and affects the development of <i>Dictyostelium discoideum</i>. DdTPS8 catalyzes the formation of a sesquiterpene discoidol, which is undetectable from the volatile bouquet of wild type <i>D. discoideum</i>. Interestingly, a <i>DdTPS8</i> knockout mutant lacks not only discoidol, but also a putative trisnorsesquiterpene. This compound was hypothesized to be derived from discoidol via cytochrome P450 (CYP)-catalyzed oxidative cleavage. <i>CYP521A1</i>, which is clustered with <i>DdTPS8</i>, was identified as a top candidate. Biochemical assays demonstrated that CYP521A1 catalyzes the conversion of discoidol to a novel trisnorsesquiterpene named discodiene. The <i>DdTPS8</i> knockout mutant exhibited slow progression in development. This study points to the untapped diversity of natural products made by <i>D. discoideum</i>, which may have diverse roles in its development and chemical ecology.