A Highly Promiscuous ß-Ketoacyl-ACP Synthase (KAS) III-like Protein Is Involved in Pactamycin Biosynthesis
| Autor: | Taifo Mahmud, Corey J. Brumsted, Benjamin Philmus, Mostafa E. Abugrain, Andrew R. Osborn |
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| Rok vydání: | 2017 |
| Předmět: |
Stereochemistry
Coenzyme A Biology 010402 general chemistry 01 natural sciences Biochemistry Catalysis chemistry.chemical_compound Biosynthesis 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase Moiety Claisen condensation ATP synthase Molecular Structure 010405 organic chemistry Pactamycin General Medicine In vitro 0104 chemical sciences chemistry Acyltransferase biology.protein Molecular Medicine lipids (amino acids peptides and proteins) |
| Zdroj: | ACS chemical biology. 12(2) |
| ISSN: | 1554-8937 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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