Title: The cysteine 703 to isoleucine or histidine mutation of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae generates an iridal-type triterpenoid
Authors: Chang, Cheng-Hsiang
Chen, Yi-Chi
Tseng, Sheng-Wei
Liu, Yuan-Ting
Wen, Hao-Yu
Li, Wen-Hsuan
Huang, Chiao-Ying
Ko, Cheng-Yu
Wang, Tsai-Ting
Wu, Tung-Kung
Department of Biological Science and Technology
Keywords: Oxidosqualene-lanosterol cyclase;Site-saturated mutagenesis;Iridal;Homology modeling;Marneral synthase
Issue Date: 1-Nov-2012
Abstract: The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7(C7031/H)) generates an unusual truncated bicyclic rearranged intermediate, (8R,9R,10R)-polypoda-5,13E,17E,21-tetraen-3 beta-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17 alpha/beta exocyclic hydrocarbon side chain, rearranged tetracyclic, and chair chair chair tricyclic intermediates (compounds 3-9), were also isolated from the ERG7(C703X) site-saturated mutations or the ERG7(F699T/C7031) 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. (C) 2012 Elsevier Masson SAS. All rights reserved.
URI: http://dx.doi.org/10.1016/j.biochi.2012.06.014
ISSN: 0300-9084
DOI: 10.1016/j.biochi.2012.06.014
Volume: 94
Issue: 11
Begin Page: 2376
End Page: 2381
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