9E2H

Variediene synthase hexameric prenyltransferase core

Summary for 9E2H

• Entry DOI: 10.2210/pdb9e2h/pdb
• EMDB information: 47452
• Descriptor: Variediene synthase (1 entity in total)
• Functional Keywords: enzyme, terpene, bifunctional, variediene, transferase
• Biological source: Aspergillus stellatus
• Total number of polymer chains: 6
• Total formula weight: 495421.50

Authors

Wenger, E.S.,Christianson, D.W. (deposition date: 2024-10-22, release date: 2025-05-21, Last modification date: 2025-12-03)

Primary citation

Wenger, E.S.,Christianson, D.W.
Structure of bifunctional variediene synthase yields unique insight on biosynthetic diterpene assembly and cyclization.
Nat Commun, 16:5089-5089, 2025

PubMed Abstract: 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.

PubMed: 40456796
DOI: 10.1038/s41467-025-60537-3

Experimental method

ELECTRON MICROSCOPY (2.77 Å)