Reconstitution of a Type II Polyketide Synthase that Catalyzes Polyene Formation. Issue 7 (17th January 2018)

• Record Type: Journal Article
• Authors: Du, Danyao; Katsuyama, Yohei; Shin‐ya, Kazuo; Ohnishi, Yasuo
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 7(2018)
• Page Start: 1954
• Page End: 1957
• Publication Date: 2018-01-17
• Subjects: biosynthesis -- polyenes -- polyketides -- Streptomyces -- polyketide synthases; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201709636
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: While type II polyketide synthases (PKSs) are known for producing aromatic compounds, a phylogenetically new subfamily of type II PKSs have been recently proposed to synthesize polyene structures. Here we report in vitro analysis of such a type II PKS, IgaPKS for ishigamide biosynthesis. The ketoreductase (Iga13) and dehydratase (Iga16) were shown to catalyze the reduction of a β‐keto group and dehydration of a β‐hydroxy group, respectively, to form a trans double bond. Incubation of the acyl carrier protein (Iga10), the ketosynthase/chain length factor complex (Iga11–Iga12), Iga13 and Iga16 with malonyl and hexanoyl‐CoAs and NADPH followed by KOH hydrolysis resulted in the formation of four unsaturated carboxylic acids (C8, C10, C12, and C14 ), indicating that IgaPKS catalyzes tetraene formation by repeating the cycle of condensation, keto‐reduction and dehydration with strict stereo‐specificity. We propose "highly reducing type II PKS subfamily" for the polyene‐producing type II PKSs. Abstract : Round round get around : While type II polyketide synthases (PKSs) are known for producing aromatic compounds, in vitro analysis of the type II PKS for ishigamide biosynthesis demonstrated that it catalyzes tetraene formation through a repeating cycle of condensation, ketoreduction, and dehydration with strict stereospecificity. This establishes a subfamily of type II PKS, namely highly reducing type II PKSs, which synthesize polyenes.