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Acyl-chain elongation drives ketosynthase substrate selectivity intrans-acyltransferase polyketide synthases
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Jenner, Matthew, Afonso, José Pedro, Bailey, Hannah R., Frank, Sarah, Kampa, Annette, Piel, Jörn and Oldham, Neil J. (2014) Acyl-chain elongation drives ketosynthase substrate selectivity intrans-acyltransferase polyketide synthases. Angewandte Chemie International Edition, 54 (6). pp. 1817-1821. doi:10.1002/anie.201410219 ISSN 1433-7851.
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Official URL: http://dx.doi.org/10.1002/anie.201410219
Abstract
ype I modular polyketide synthases (PKSs), which are responsible for the biosynthesis of many biologically active agents, possess a ketosynthase (KS) domain within each module to catalyze chain elongation. Acylation of the KS active site Cys residue is followed by transfer to malonyl‐ACP to yield an extended β‐ketoacyl chain (ACP=acyl carrier protein). To date, the precise contribution of KS selectivity in controlling product fidelity has been unclear. Six KS domains from trans‐acyltransferase (trans‐AT) PKSs were subjected to a mass spectrometry based elongation assay, and higher substrate selectivity was identified for the elongating step than in preceding acylation. A close correspondence between the observed KS selectivity and that predicted by phylogenetic analysis was seen. These findings provide insights into the mechanism of KS selectivity in this important group of PKSs, can serve as guidance for engineering, and show that targeted mutagenesis can be used to expand the repertoire of acceptable substrates.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||
Journal or Publication Title: | Angewandte Chemie International Edition | ||||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||||
ISSN: | 1433-7851 | ||||||
Official Date: | 21 December 2014 | ||||||
Dates: |
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Volume: | 54 | ||||||
Number: | 6 | ||||||
Page Range: | pp. 1817-1821 | ||||||
DOI: | 10.1002/anie.201410219 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access |
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