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Structural Insights Into Anthranilate Priming During Type II Polyketide Biosynthesis

Jackson, David R. and Tu, Stephanie S. and Nguyen, MyChi and Barajas, Jesus F. and Krug, Daniel and Pistorius, Dominik and Müller, Rolf and Tsai, Shiou-Chuan (2015) Structural Insights Into Anthranilate Priming During Type II Polyketide Biosynthesis. Biochemistry, 11 (1). pp. 95-103. ISSN 1554-89291554-8937

Abstract

The incorporation of non-acetate starter units during type II polyketide biosynthesis helps diversify natural products. Currently, there are few enzymatic strategies for the incorporation of non-acetate starter units in type II PKS pathways. Here we report the crystal structure of AuaEII, the anthranilate:CoA ligase responsible for the generation of anthranoyl-CoA, which is used as a starter unit by a type II PKS during aurachin biosynthesis. We present structural and protein sequence comparisons to other aryl:CoA ligases. We also compare the AuaEII crystal structure to a model of a CoA ligase homologue, AuaE, which is present in the same gene cluster. AuaE is predicted to have the same fold as AuaEII, but instead of CoA ligation, AuaE catalyzes acyl transfer of anthranilate from anthranoyl-CoA to the acyl carrier protein (ACP). Together, this work provides insight into the molecular basis for starter unit selection of anthranilate during type II PKS biosynthesis.

Item Type: Article
Date Deposited: 25 Apr 2016 23:45
Last Modified: 04 Jul 2016 23:45
URI: https://oak.novartis.com/id/eprint/24855

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