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Publication Abstract from PubMed

Terpene synthases produce a remarkable structural diversity from acyclic precursors through complex carbocation cascades. Here, we report the crystal structure of the bacterial sesterterpene synthase StvirS bound to geranylfarnesyl thiopyrophosphate (GFSPP), revealing a preorganized active site that enforces a defined folding of the C25 backbone. Guided by this structure, active-site engineering at 11 positions yielded 23 enzyme variants and 13 new sesterterpenes. Specific substitutions altered reaction trajectories, stereochemistry, or induced premature termination, emphasizing the sensitivity of StvirS to subtle structural changes. Isotopic labeling established the absolute configurations of 11 products and experimentally confirmed a conserved cyclization pathway. These results illustrate how precise noncovalent interactions govern terpene biosynthesis and highlight the promise of structure-based design to reprogram terpene cyclase reactivity.

Structure-Guided Engineering of a Bacterial Sesterterpene Synthase for Sesterviridene Diversification.,Li H, Troycke P, Yin Z, Groll M, Dickschat JS J Am Chem Soc. 2025 Sep 11. doi: 10.1021/jacs.5c11309. PMID:40931719^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.