Sesterviridene synthase (StvirS) (StvirS)

Bacterial sesterterpene synthase StvirS is an enzyme originating from the actinobacterium Kitasatospora viridis that specializes in the biosynthesis of sesterterpenes, a rare and structurally diverse class of C25 isoprenoids [4]. It catalyzes the complex cyclization of geranylfarnesyl diphosphate (GFPP) to form sesterviridene A, a reaction involving a sophisticated carbocation cascade initiated by the ionization of the substrate's diphosphate group [1][4]. The enzyme's crystal structure reveals a highly organized active site that meticulously controls the folding and stereochemistry of the acyclic precursor, facilitating multiple ring closures [1]. Research on StvirS has demonstrated significant catalytic plasticity, as structure-guided engineering can reprogram its reactivity to produce a variety of non-native sesterterpenoid scaffolds [1][3]. While it is not currently a direct therapeutic target for treating human diseases, StvirS serves as a critical model in natural product discovery and synthetic biology for generating novel bioactive molecules [6][11]. Its mechanistic study provides fundamental insights into how terpene cyclases manage high-energy intermediates to achieve remarkable structural complexity from simple precursors [1][4].

Other names

Bacterial sesterterpene synthase StvirSSesterviridene A synthaseSesterterpene cyclaseKitasatospora viridis sesterterpene synthase

As a class I sesterterpene synthase, StvirS catalyzes the cyclization of geranylfarnesyl diphosphate (GFPP) via a carbocation cascade. The reaction is initiated by the metal-dependent ionization of the diphosphate group, followed by a sequence of substrate-controlled ring closures and rearrangements that are directed by the enzyme's preorganized active site to yield the hydrocarbon sesterviridene A [1][4].