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Issue 3, 2016
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Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein

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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.

Graphical abstract: Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein

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Publication details

The article was received on 12 Oct 2015, accepted on 08 Dec 2015 and first published on 10 Dec 2015


Article type: Edge Article
DOI: 10.1039/C5SC03864B
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Citation: Chem. Sci., 2016,7, 1779-1785
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    Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein

    X. Dong, C. D. Bailey, C. Williams, J. Crosby, T. J. Simpson, C. L. Willis and M. P. Crump, Chem. Sci., 2016, 7, 1779
    DOI: 10.1039/C5SC03864B

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