Organic Letters
Organic Letters
5 years ago

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

Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway
Shu-Shan Gao, Yi Zou, Yiu-Sun Hung, Leibniz Hang, Nicholas Liu, Yi Tang, Yit-Heng Chooi
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.

Publisher URL: http://dx.doi.org/10.1021/acs.orglett.7b01534

DOI: 10.1021/acs.orglett.7b01534

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