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

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• 作者：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
• 关键词：Oxidosqualene-lanosterol cyclase ; Site-saturated mutagenesis ; Iridal ; Homology modeling ; Marneral synthase
• 刊名：Biochimie
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：94
• 期：11
• 页码：2376-2381
• 全文大小：539 K

文摘

The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7^C703I/H) generates an unusual truncated bicyclic rearranged intermediate, (8R,9R,10R)-polypoda-5,13E,17E,21-tetraen-3¦Â-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17¦Á/¦Â 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/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.