Title: A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis
Authors: Haines, Anthony S
Song, Zhongshu
Farmer, Rohit
Williams, Christopher
Hothersall, Joanne
Płoskoń, Eliza
Wattana-Amorn, Pakorn
Stephens, Elton R
Yamada, Erika
Gurney, Rachel
Takebayashi, Yuiko
Masschelein, Joleen
Cox, Russell J
Lavigne, Rob
Willis, Christine L
Simpson, Thomas J
Crosby, John
Winn, Peter J
Thomas, Christopher M
Crump, Matthew P # ×
Issue Date: Nov-2013
Publisher: Nature Pub. Group
Series Title: Nature chemical biology vol:9 issue:11 pages:685-92
Article number: 10.1038/nchembio.1342
Abstract: Type I polyketide synthases often use programmed β-branching, via enzymes of a 'hydroxymethylglutaryl-CoA synthase (HCS) cassette', to incorporate various side chains at the second carbon from the terminal carboxylic acid of growing polyketide backbones. We identified a strong sequence motif in acyl carrier proteins (ACPs) where β-branching is known to occur. Substituting ACPs confirmed a correlation of ACP type with β-branching specificity. Although these ACPs often occur in tandem, NMR analysis of tandem β-branching ACPs indicated no ACP-ACP synergistic effects and revealed that the conserved sequence motif forms an internal core rather than an exposed patch. Modeling and mutagenesis identified ACP helix III as a probable anchor point of the ACP-HCS complex whose position is determined by the core. Mutating the core affects ACP functionality, whereas ACP-HCS interface substitutions modulate system specificity. Our method for predicting β-carbon branching expands the potential for engineering new polyketides and lays a basis for determining specificity rules.
ISSN: 1552-4450
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Division of Gene Technology (-)
× corresponding author
# (joint) last author

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