Semisynthesis of Plant-Derived Englerin A Enabled by Microbe Engineering of Guaia-6,10(14)-diene as Building Block.

Thomas Siemon, Zhangqian Wang, Guangkai Bian, Tobias Seitz, Ziling Ye, Yan Lu, Shu Cheng, Yunkun Ding, Yanglei Huang, Zixin Deng, Tiangang Liu, Mathias Christmann

Journal of the American Chemical Society 2020 Feb 12

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Herein, we report a short semisynthesis of the potent transient receptor potential canonical (TRPC) channel agonist englerin A (EA) and the related guaianes oxyphyllol and orientalol E. The guaia-6,10(14)-diene starting material was systematically engineered in Escherichia coli and Saccharomyces cerevisiae using the CRISPR/Cas9 system and was produced with high titers. The potentially scalable approach combines the advantages of synthetic biology and chemical synthesis providing an efficient and economical method for producing EA and analogues.

Citation

Thomas Siemon, Zhangqian Wang, Guangkai Bian, Tobias Seitz, Ziling Ye, Yan Lu, Shu Cheng, Yunkun Ding, Yanglei Huang, Zixin Deng, Tiangang Liu, Mathias Christmann. Semisynthesis of Plant-Derived Englerin A Enabled by Microbe Engineering of Guaia-6,10(14)-diene as Building Block. Journal of the American Chemical Society. 2020 Feb 12;142(6):2760-2765