Issue 3, 2016

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

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

Supplementary files

Article information

Article type
Edge Article
Submitted
12 Oct 2015
Accepted
08 Dec 2015
First published
10 Dec 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 1779-1785

Author version available

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements