7VTB

Partially closed conformation of talaropentaene synthase cyclase domain

Summary for 7VTB

• Entry DOI: 10.2210/pdb7vtb/pdb
• Descriptor: TvTS cyclase domain, NICKEL (II) ION (3 entities in total)
• Functional Keywords: talaromyces verruculosus, talaropentaene synthase, triterpene, transferase
• Biological source: Talaromyces verruculosus
• Total number of polymer chains: 1
• Total formula weight: 37046.18

Authors

Hui, T.,Mori, T.,Abe, I. (deposition date: 2021-10-28, release date: 2022-06-08, Last modification date: 2023-11-29)

Primary citation

Tao, H.,Lauterbach, L.,Bian, G.,Chen, R.,Hou, A.,Mori, T.,Cheng, S.,Hu, B.,Lu, L.,Mu, X.,Li, M.,Adachi, N.,Kawasaki, M.,Moriya, T.,Senda, T.,Wang, X.,Deng, Z.,Abe, I.,Dickschat, J.S.,Liu, T.
Discovery of non-squalene triterpenes.
Nature, 606:414-419, 2022

PubMed Abstract: All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene. This approach is fundamentally different from the biosynthesis of short-chain (C-C) terpenes that are formed from polyisoprenyl diphosphates. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate and isopentenyl diphosphate or hexaprenyl diphosphate as substrates, representing the first examples, to our knowledge, of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms of TvTS and MpMS and the absolute configurations of their products were investigated in isotopic labelling experiments. Structural analyses of the terpene cyclase domain of TvTS and full-length MpMS provide detailed insights into their catalytic mechanisms. An AlphaFold2-based screening platform was developed to mine a third TrTS, Colletotrichum gloeosporioides colleterpenol synthase (CgCS). Our findings identify a new enzymatic mechanism for the biosynthesis of triterpenes and enhance understanding of terpene biosynthesis in nature.

PubMed: 35650436
DOI: 10.1038/s41586-022-04773-3

Experimental method

X-RAY DIFFRACTION (2 Å)