Complete Pathway Elucidation and Heterologous Reconstitution of Rhodiola Salidroside Biosynthesis

作     者：Michael P. Torrens-Spence Tomas Pluskal Fu-Shuang Li Valentina Carballo Jing-Ke Weng 

作者机构：Whitehead Institute for Biomedical Research 455 Main Street Cambridge MA 02142 USA Department of Biology Massachusetts Institute of Technology Cambridge MA USA 

出 版 物：《Molecular Plant》 (分子植物（英文版）)

年 卷 期：2018年第11卷第1期

页      面：205-217页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 080203[工学-机械设计及理论] 0901[农学-作物学] 0802[工学-机械工程] 0902[农学-园艺学] 080201[工学-机械制造及其自动化] 

基　　金：supported by the Pew Scholar Program in the Biomedical Sciences (J.-K.W.) Searle Scholars Program (J.-K.W.) 

主　　题：salidroside icariside D2 4-hydroxyphenylacetaldehyde tyrosol aromatic acetaldehyde synthesis aromatic amino acid decarboxylase 

摘      要：Salidroside is a bioactive tyrosine-derived phenolic natural product found in medicinal plants under the Rhodiola genus. In addition to their anti-fatigue and anti-anoxia roles in traditional medicine, Rhodiola total extract and salidroside have also displayed medicinal properties as anti-cardiovascular diseases and anticancer agents. The resulting surge in global demand of Rhodiola plants and salidroside has driven some species close to extinction. Here, we report the full elucidation of the Rhodiola salidroside biosynthetic pathway utilizing the first comprehensive transcriptomics and metabolomics datasets for Rhodiola rosea. Unlike the previously proposed pathway involving separate decarboxylation and deamination enzymatic steps from tyrosine to the key intermediate 4-hydroxyphenylacetaldehyde （4-HPAA）, Rhodiola contains a pyridoxal phosphate-dependent 4-HPAA synthase that directly converts tyrosine to 4-HPAA. We further identified genes encoding the subsequent 4-HPAA reductase and tyrosohUDP-glucose 8-O-glucosyltransferase, respectively, to complete salidroside biosynthesis in Rhodiola. We show that heterologous production of salidroside can be achieved in the yeast Saccharomyces cerevisiae as well as the plant Nicotiana benthamiana through transgenic expression of Rhodiola salidroside biosynthetic genes. This study provides new tools for engineering sustainable production of salidroside in heterologous hosts.