Vinigrol Tricyclic Scaffold Biosynthesis Employs an Atypical Terpene Cyclase and a Multipotent Cyclization Cascade.

ABSTRACT: Vinigrol (1) is a fungal diterpenoid consisting of a decahydro-1,5-butanonaphthalene ring system with no analogs in nature. Despite immense efforts in synthetic studies, the vinigrol biosynthesis pathway remains largely unknown. Herein, we identified a biosynthetic gene cluster for 1 and fully elucidated the biosynthetic pathway. By employing an AlphaFold-generated model structure, we identified the possible catalytic residues of the noncanonical terpene cyclase and analyzed their function by site-directed mutagenesis. We found that the G340A mutation opened a cryptic pathway for an unprecedented tetracyclic diterpene, defined here as virgarene. Retro-biosynthetic theoretical analysis provided a solid foundation for the complex cyclization pathway for the vinigrol scaffold, i

SUBMITTER: Tsukada K 

PROVIDER: S-EPMC12703729 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature