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Discovery of non-squalene triterpenes
Hui Tao1, Lukas Lauterbach2, Guangkai Bian3
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Nature
|June 1, 2022
Summary
Researchers discovered novel fungal enzymes that create triterpenes without squalene. This finding reveals a new pathway for triterpene biosynthesis, expanding our understanding of natural terpene production.
Area of Science:
- Biochemistry
- Enzymology
- Natural Product Biosynthesis
Background:
- Triterpenes are typically synthesized from squalene or oxidosqualene by triterpene synthases (TrTSs).
- Short-chain terpenes (C10-C25) are formed via polyisoprenyl diphosphates, a distinct pathway.
Purpose of the Study:
- To characterize two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS).
- To investigate a novel, non-squalene-dependent pathway for triterpene biosynthesis.
Main Methods:
- Enzymatic characterization of TvTS and MpMS using dimethylallyl diphosphate, isopentenyl diphosphate, and hexaprenyl diphosphate.
- Isotopic labeling experiments to determine cyclization mechanisms and product configurations.
- Structural analysis of terpene cyclase domains.
- AlphaFold2-based screening for identifying new TrTSs.
Main Results:
- TvTS and MpMS were identified as the first examples of non-squalene-dependent triterpene biosynthesis.
- Detailed insights into the catalytic mechanisms of TvTS and MpMS were obtained.
- A new triterpene synthase, Colletotrichum gloeosporioides colleterpenol synthase (CgCS), was identified using computational screening.
Conclusions:
- A novel enzymatic mechanism for triterpene biosynthesis has been discovered.
- This research significantly enhances the understanding of diverse terpene biosynthesis pathways in nature.
