Isolation of Artemisia capillaris membrane-bound di-prenyltransferase for phenylpropanoids and redesign of artepillin C in yeast
Isolation of Artemisia capillaris membrane-bound di-prenyltransferase for phenylpropanoids and redesign of artepillin C in yeast
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DOI：
10.1038/s42003-019-0630-0
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发表时间：
2019-10
影响因子：
5.9
通讯作者：
R. Munakata;Tomoya Takemura;Kanade Tatsumi;Eiko Moriyoshi;Koki Yanagihara;A. Sugiyama;Hideyuki Suzuki;H. Seki;T. Muranaka;N. Kawano;K. Yoshimatsu;N. Kawahara;T. Yamaura;Jérémy Grosjean;F. Bourgaud;A. Hehn;K. Yazaki
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文献类型：
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作者：
R. Munakata;Tomoya Takemura;Kanade Tatsumi;Eiko Moriyoshi;Koki Yanagihara;A. Sugiyama;Hideyuki Suzuki;H. Seki;T. Muranaka;N. Kawano;K. Yoshimatsu;N. Kawahara;T. Yamaura;Jérémy Grosjean;F. Bourgaud;A. Hehn;K. Yazaki
植物产生各种异戊烯化的酚类代谢物，包括类黄酮、间苯三酚和香豆素，其中许多具有多个异戊烯基部分并显示出各种生物活性。异戊烯化的苯基丙烷，如阿替匹林C（3，5-二异戊烯基-对香豆酸），表现出广泛的药物作用。然而，迄今为止，没有异戊二烯基转移酶（PT）参与苯丙烷的生物合成，并没有植物酶，引入多个异戊二烯残基的天然底物具有不同的区域特异性已被确定。本研究从茵陈蒿中克隆了一个苯丙烷特异的PT基因AcPT 1，该基因属于UbiA超家族。该基因编码一种膜结合酶，该酶接受β-香豆酸作为其特异性底物，并逐步转移两个异戊二烯残基以产生阿替匹林C。这些发现为该基因家族的分子进化提供了新的见解，有助于植物专门代谢物的化学多样化。这些结果还使得能够设计用于合成生物学的阿替匹林C的酵母平台。
Plants produce various prenylated phenolic metabolites, including flavonoids, phloroglucinols, and coumarins, many of which have multiple prenyl moieties and display various biological activities. Prenylated phenylpropanes, such as artepillin C (3,5-diprenyl-p-coumaric acid), exhibit a broad range of pharmaceutical effects. To date, however, no prenyltransferases (PTs) involved in the biosynthesis of phenylpropanes and no plant enzymes that introduce multiple prenyl residues to native substrates with different regio-specificities have been identified. This study describes the isolation fromArtemisia capillarisof a phenylpropane-specific PT gene,AcPT1, belonging to UbiA superfamily. This gene encodes a membrane-bound enzyme, which acceptsp-coumaric acid as its specific substrate and transfers two prenyl residues stepwise to yield artepillin C. These findings provide novel insights into the molecular evolution of this gene family, contributing to the chemical diversification of plant specialized metabolites. These results also enabled the design of a yeast platform for the synthetic biology of artepillin C.