Structural Insights into Anthranilate Priming during Type II Polyketide Biosynthesis

详细信息    查看全文

• 作者：David R. Jackson ; Stephanie S. Tu ; MyChi Nguyen ; Jesus F. Barajas ; Andrew J. Schaub ; Daniel Krug ; Dominik Pistorius ; Ray Luo ; Rolf Müller ; Shiou-Chuan Tsai
• 刊名：ACS Chemical Biology
• 出版年：2016
• 出版时间：January 15, 2016
• 年：2016
• 卷：11
• 期：1
• 页码：95-103
• 全文大小：515K
• ISSN：1554-8937

文摘

The incorporation of nonacetate starter units during type II polyketide biosynthesis helps diversify natural products. Currently, there are few enzymatic strategies for the incorporation of nonacetate starter units in type II polyketide synthase (PKS) pathways. Here we report the crystal structure of AuaEII, the anthranilate:CoA ligase responsible for the generation of anthraniloyl-CoA, which is used as a starter unit by a type II PKS in 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 anthraniloyl-CoA to the acyl carrier protein (ACP). Together, this work provides insight into the molecular basis for starter unit selection of anthranilate in type II PKS biosynthesis.