Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

文献类型： 外文期刊

第一作者： Zhao, Yucheng

作者： Zhao, Yucheng;Zhang, Libo;Zhao, Yucheng;Zhang, Libo;Xiao, Yibei;He, Yuedong;Han, Liangliang;Xia, Yuanzheng;Yin, Fucheng;Wang, Xiaobing;Kong, Lingyi;Han, Liangliang;Xia, Yuanzheng;Yin, Fucheng;Wang, Xiaobing;Kong, Lingyi;Zhao, Deqing;Qiao, Fei;Xu, Sheng;Xiao, Yibei

作者机构：

关键词： Tetrahydropyrans; Tetrahydrofurans; Baldwin rules; Coumarins; CYP450 cyclase

期刊名称：ACTA PHARMACEUTICA SINICA B （ 影响因子：14.5； 五年影响因子：13.2 ）

ISSN： 2211-3835

年卷期： 2024 年 14 卷 2 期

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收录情况： SCI

摘要： Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme -catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site -specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chem- ically diverse in terms of enzyme function and catalytic process. 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY -NC - ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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