Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway

作者：Nicholas Liu, Yiu‐Sun Hung, Shu‐Shan Gao, Leibniz Hang, Yi Zou, Yit‐Heng Chooi, Yi Tang · 发表于：Organic Letters · 年份：2017 · DOI：10.1021/acs.orglett.7b01534 · 被引用次数：137 · 研究领域：Microbial Natural Products and Biosynthesis、Fungal Biology and Applications、Plant biochemistry and biosynthesis

Zaragozic acid A (1) is a potent cholesterol lowering, polyketide natural product made by various filamentous fungi. The reconstitution of enzymes responsible for the initial steps of the biosynthetic pathway of 1 is accomplished using an engineered fungal heterologous host. These initial steps feature the priming of a benzoic acid starter unit onto a highly reducing polyketide synthase (HRPKS), followed by oxaloacetate extension and product release to generate a tricarboxylic acid containing product 2. The reconstitution studies demonstrated that only three enzymes, HRPKS, citrate synthase, and hydrolase, are needed in A. nidulans to produce the structurally complex product.