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在绿胶霉素生物合成中氧化还原酶对化学多样性的组合生成

Combinatorial Generation of Chemical Diversity by Redox Enzymes in Chaetoviridin Biosynthesis.

作者信息

Sato Michio, Winter Jaclyn M, Kishimoto Shinji, Noguchi Hiroshi, Tang Yi, Watanabe Kenji

机构信息

Department of Pharmaceutical Sciences, University of Shizuoka , Shizuoka 422-8526, Japan.

Department of Chemical and Biomolecular Engineering, University of California , Los Angeles, California 90095, United States.

出版信息

Org Lett. 2016 Mar 18;18(6):1446-9. doi: 10.1021/acs.orglett.6b00380. Epub 2016 Mar 9.

Abstract

Chaetoviridins constitute a large family of structurally related secondary metabolites isolated from Chaetomium fungi. To elucidate the biosynthesis pathway and understand how the chemical diversity of chaetoviridins is generated, gene deletion and in vitro characterization of the four post-PKS modifications enzymes were undertaken. CazL and CazP were identified to have substrate promiscuity that facilitates the formation of nonchlorinated analogues. In addition, enzymatic oxidation and reduction combined with spontaneous dehydration and lactonization of the intermediates further expand the chemical diversity.

摘要

绿毛壳菌素是从毛壳菌中分离出的一大类结构相关的次生代谢产物。为阐明其生物合成途径并了解绿毛壳菌素的化学多样性是如何产生的,我们对四种聚酮合酶后修饰酶进行了基因缺失和体外表征研究。已确定CazL和CazP具有底物混杂性,这有助于形成非氯化类似物。此外,酶促氧化和还原作用,再加上中间体的自发脱水和内酯化作用,进一步扩大了化学多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9450/4903021/12a8606b1820/nihms-793058-f0002.jpg

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