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TitleStructure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 5089, Year 2025
Publish dateJun 2, 2025
AuthorsEliott S Wenger / David W Christianson /
PubMed AbstractAn unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C geranylgeranyl diphosphate (GGPP), which is then converted ...An unusual family of bifunctional terpene synthases has been identified in which a prenyltransferase assembles 5-carbon precursors to form C geranylgeranyl diphosphate (GGPP), which is then converted into a polycyclic product by a cyclase. Here, we report the cryo-EM structure of a massive, 495-kD bifunctional terpene synthase, variediene synthase from Emericella variecolor (EvVS). The structure reveals a hexameric prenyltransferase core sandwiched between two triads of cyclases. Surprisingly, GGPP is not channeled intramolecularly from the prenyltransferase to the cyclase, but instead is channeled intermolecularly to a non-native cyclase as indicated by substrate competition experiments. These results inform our understanding of carbon management in the greater family of bifunctional terpene synthases, hundreds of which have been identified in fungi. Using sequence similarity networks, we also report the identification of bifunctional terpene synthases in an animal, Adineta steineri, a bdelloid rotifer indigenous to freshwater environments.
External linksNat Commun / PubMed:40456796 / PubMed Central
MethodsEM (single particle)
Resolution2.77 - 3.59 Å
Structure data

47452

9e2h

EMDB-47452, PDB-9e2h:
Variediene synthase hexameric prenyltransferase core
Method: EM (single particle) / Resolution: 2.77 Å

47453

9e2i

EMDB-47453, PDB-9e2i:
Variediene synthase with six cyclases
Method: EM (single particle) / Resolution: 3.18 Å

47454

9e2j

EMDB-47454, PDB-9e2j:
Variediene synthase with five cyclases
Method: EM (single particle) / Resolution: 3.59 Å

47455

9e2k

EMDB-47455, PDB-9e2k:
Variediene synthase with one cyclase (conformation 1)
Method: EM (single particle) / Resolution: 3.0 Å

47456

9e2l

EMDB-47456, PDB-9e2l:
Variediene synthase with one cyclase (conformation 2)
Method: EM (single particle) / Resolution: 3.08 Å

47457

9e2m

EMDB-47457, PDB-9e2m:
Variediene synthase with one cyclase (conformation 3)
Method: EM (single particle) / Resolution: 2.98 Å

Chemicals

ChemComp-POP:
PYROPHOSPHATE 2-

Source
  • aspergillus stellatus (mold)
KeywordsTRANSFERASE / Enzyme / terpene / bifunctional / variediene

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