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

Nicholas Liu, Yiu Sun Hung, Shu Shan Gao, Leibniz Hang, Yi Zou, Yit Heng Chooi, Yi Tang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3560-3563
Number of pages4
JournalOrganic Letters
Volume19
Issue number13
DOIs
Publication statusPublished - 7 Jul 2017

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