Promiscuous Oxidosqualene Cyclases from Catalyzing the Formation of Tetracyclic, Pentacyclic, and Heterocyclic Triterpenes.

Org Lett

National-Local Joint Engineering Research Center on Gemplasm Innovation & Utilization of Chinese Medicinal Materials in Southwest, The Key Laboratory of Medicinal Plant Biology of Yunnan Province, Yunnan Agricultural University, Kunming, Yunnan 650201, China.

Published: April 2024

AI Article Synopsis

  • - Six different oxidosqualene cyclases (OSC1-OSC6) were studied for their role in creating various triterpene structures, including both tetracyclic and pentacyclic forms from two starting materials: 2,3-oxidosqualene and 2,3:22,23-dioxidosqualene.
  • - OSC1 was particularly effective at producing rare (20)-epimers of oxacyclic triterpenes, and a mutant version of OSC1 (F731G) significantly enhanced the production of these (20)-epimers compared to the normal OSC1.
  • - The study utilized homology modeling and molecular docking techniques to explain how the (20)-configuration develops during the epoxide

Article Abstract

Six oxidosqualene cyclases (OSC1-OSC6) from were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene () and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (). OSC1 showed high efficiency in the production of naturally rare (20)-epimers of oxacyclic triterpenes. Mutagenesis results revealed that the OSC1-F731G mutant significantly increased the yields of (20)-epimers compared to the wild type. Homology modeling and molecular docking elucidated the origin of the (20)-configuration in the epoxide addition step.

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http://dx.doi.org/10.1021/acs.orglett.4c00730DOI Listing

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