The cysteine 703 to isoleucine or histidine mutation of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae generates an iridal-type triterpenoid

Cheng Hsiang Chang, Yi Chi Chen, Sheng Wei Tseng, Yuan Ting Liu, Hao Yu Wen, Wen Hsuan Li, Chiao Ying Huang, Cheng Yu Ko, Tsai Ting Wang, Tung-Kung Wu*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7C703I/H) generates an unusual truncated bicyclic rearranged intermediate, (8R,9R,10R)-polypoda-5,13E, 17E,21-tetraen-3β-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17α/β exocyclic hydrocarbon side chain, rearranged tetracyclic, and chair-chair-chair tricyclic intermediates (compounds 3-9), were also isolated from the ERG7C703X site-saturated mutations or the ERG7F699T/C703I double mutation, indicating the functional role of the Cys703 residue in stabilizing the bicyclic C-8 cation and the rearranged intermediate or interacting with Phe699, and opened a new avenue of engineering ERG7 for producing biological active agents.

Original languageEnglish
Pages (from-to)2376-2381
Number of pages6
JournalBiochimie
Volume94
Issue number11
DOIs
StatePublished - 1 Nov 2012

Keywords

  • Homology modeling
  • Iridal
  • Marneral synthase
  • Oxidosqualene-lanosterol cyclase
  • Site-saturated mutagenesis

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