In Vitro Analysis of Carboxyacyl Substrate Tolerance in the Loading and First Extension Modules of Borrelidin Polyketide Synthase

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• 作者：Andrew Hagen ; Sean Poust ; Tristan de Rond ; Satoshi Yuzawa ; Leonard Katz ; Paul D. Adams ; Christopher J. Petzold ; Jay D. Keasling
• 刊名：Biochemistry
• 出版年：2014
• 出版时间：September 30, 2014
• 年：2014
• 卷：53
• 期：38
• 页码：5975-5977
• 全文大小：203K
• ISSN：1520-4995

文摘

The borrelidin polyketide synthase (PKS) begins with a carboxylated substrate and, unlike typical decarboxylative loading PKSs, retains the carboxy group in the final product. The specificity and tolerance of incorporation of carboxyacyl substrate into type I PKSs have not been explored. Here, we show that the first extension module is promiscuous in its ability to extend both carboxyacyl and non-carboxyacyl substrates. However, the loading module has a requirement for substrates containing a carboxy moiety, which are not decarboxylated in situ. Thus, the loading module is the basis for the observed specific incorporation of carboxylated starter units by the borelidin PKS.