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Recognition of extended linear and cyclised polyketide mimics by a Type II acyl carrier protein

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Original languageEnglish
Pages (from-to)1779-1785
Number of pages7
JournalChemical Science
Volume7
Issue number3
Early online date10 Dec 2015
DOIs
DateAccepted/In press - 8 Dec 2015
DateE-pub ahead of print - 10 Dec 2015
DatePublished (current) - 1 Mar 2016

Abstract

Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP’s capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs.

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via RSC at http://pubs.rsc.org/en/Content/ArticleLanding/2016/SC/C5SC03864B#!divAbstract. Please refer to any applicable terms of use of the publisher.

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