A Highly Promiscuous ß-Ketoacyl-ACP Synthase (KAS) III-like Protein Is Involved in Pactamycin Biosynthesis
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- 作者：Mostafa E. Abugrain ; Corey J. Brumsted ; Andrew R. Osborn ; Benjamin PhilmusTaifo Mahmud
- 刊名：ACS Chemical Biology
- 出版年：2017
- 出版时间：February 17, 2017
- 年：2017
- 卷：12
- 期：2
- 页码：362-366
- 全文大小：367K
- ISSN：1554-8937
文摘
β-Ketoacyl–acyl carrier protein (β-Ketoacyl-ACP) synthase (KAS) III catalyzes the first step in fatty acid biosynthesis, involving a Claisen condensation of the acetyl-CoA starter unit with the first extender unit, malonyl-ACP, to form acetoacetyl-ACP. KAS III-like proteins have also been reported to catalyze acyltransferase reactions using coenzyme A esters or discrete ACP-bound substrates. Here, we report the in vivo and in vitro characterizations of a KAS III-like protein (PtmR), which directly transfers a 6-methylsalicylyl moiety from an iterative type I polyketide synthase to an aminocyclopentitol unit in pactamycin biosynthesis. PtmR is highly promiscuous, recognizing a wide array of S-acyl-N-acetylcysteamines as substrates to produce a suite of pactamycin derivatives with diverse alkyl and aromatic features. The results suggest that KAS III-like proteins may be used as versatile tools for modifications of complex natural products.