两种甲基转移酶介导香豆素生物合成中的多个甲基化步骤。

Two -Methyltransferases Mediate Multiple Methylation Steps in the Biosynthesis of Coumarins in .

机构信息

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

National Center of Technology Innovation for Synthetic Biology, Tianjin 300308, China.

出版信息

J Nat Prod. 2022 Aug 26;85(8):2116-2121. doi: 10.1021/acs.jnatprod.2c00410. Epub 2022 Aug 5.

DOI:10.1021/acs.jnatprod.2c00410

PMID:35930697

Abstract

Coumarins with methoxy groups such as osthole (), xanthotoxin (), bergapten (), and isopimpinellin () are typical bioactive ingredients of many medicinal plants. The methylation steps remain widely unknown. Herein, we report the discovery of two methyltransferases in the biosynthesis of -methyl coumarins in by transcriptome mining, heterologous expression, and in vitro enzymatic assays. The results reveal that (i) CmOMT1 catalyzes the methylation of osthenol () as the final step in the biosynthesis of , (ii) CmOMT2 shows the highest efficiency and preference for methylating xanthotoxol () to form , and (iii) CmOMT1 and CmOMT2 also efficiently transform bergaptol () and 8-hydroxybergapten () into or , suggesting the CmOMTs mediate multistep methylations in the biosynthesis of linear furanocoumarins in . .

摘要

具有甲氧基的香豆素类化合物，如蛇床子素（osthole ()）、花椒毒素（xanthotoxin ()）、佛手柑内酯（bergapten ()）和异茴芹素（isopimpinellin ()），是许多药用植物中典型的生物活性成分。然而，这些化合物的甲基化步骤仍然知之甚少。本研究通过转录组挖掘、异源表达和体外酶促反应，报告了在中发现的两种 -甲基香豆素生物合成中的甲基转移酶。研究结果揭示：（i）CmOMT1 催化 osthenol ()的甲基化，作为生物合成的最后一步；（ii）CmOMT2 对甲基化 xanthotoxol ()形成具有最高的效率和偏好性；（iii）CmOMT1 和 CmOMT2 还能有效地将 bergaptol ()和 8-羟基佛手柑内酯 ()转化为或，表明 CmOMTs 介导了线性呋喃香豆素生物合成中的多步甲基化。