A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis

Research output: Contribution to journalArticlepeer-review

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A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis. / Haines, Anthony S; Dong, Xu; 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.

In: Nature Chemical Biology, Vol. 9, No. 11, 11.2013, p. 685-692.

Research output: Contribution to journalArticlepeer-review

Harvard

Haines, AS, Dong, X, Song, Z, Farmer, R, Williams, C, Hothersall, J, Płoskoń, E, Wattana-amorn, P, Stephens, ER, Yamada, E, Gurney, R, Takebayashi, Y, Masschelein, J, Cox, RJ, Lavigne, R, Willis, CL, Simpson, TJ, Crosby, J, Winn, PJ, Thomas, CM & Crump, MP 2013, 'A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis', Nature Chemical Biology, vol. 9, no. 11, pp. 685-692. https://doi.org/10.1038/nchembio.1342

APA

Haines, A. S., Dong, X., Song, Z., Farmer, R., Williams, C., Hothersall, J., Płoskoń, E., Wattana-amorn, P., Stephens, E. R., Yamada, E., Gurney, R., Takebayashi, Y., Masschelein, J., Cox, R. J., Lavigne, R., Willis, C. L., Simpson, T. J., Crosby, J., Winn, P. J., ... Crump, M. P. (2013). A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis. Nature Chemical Biology, 9(11), 685-692. https://doi.org/10.1038/nchembio.1342

Vancouver

Author

Haines, Anthony S ; Dong, Xu ; 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. / A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis. In: Nature Chemical Biology. 2013 ; Vol. 9, No. 11. pp. 685-692.

Bibtex

@article{2d17a17ed1b347709620fb9f889ba237,
title = "A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis",
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.",
author = "Haines, {Anthony S} and Xu Dong and Zhongshu Song and Rohit Farmer and Christopher Williams and Joanne Hothersall and Eliza P{\l}osko{\'n} and Pakorn Wattana-amorn and Stephens, {Elton R} and Erika Yamada and Rachel Gurney and Yuiko Takebayashi and Joleen Masschelein and Cox, {Russell J} and Rob Lavigne and Willis, {Christine L} and Simpson, {Thomas J} and John Crosby and Winn, {Peter J} and Thomas, {Christopher M} and Crump, {Matthew P}",
year = "2013",
month = nov,
doi = "10.1038/nchembio.1342",
language = "English",
volume = "9",
pages = "685--692",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "11",

}

RIS

TY - JOUR

T1 - A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis

AU - Haines, Anthony S

AU - Dong, Xu

AU - Song, Zhongshu

AU - Farmer, Rohit

AU - Williams, Christopher

AU - Hothersall, Joanne

AU - Płoskoń, Eliza

AU - Wattana-amorn, Pakorn

AU - Stephens, Elton R

AU - Yamada, Erika

AU - Gurney, Rachel

AU - Takebayashi, Yuiko

AU - Masschelein, Joleen

AU - Cox, Russell J

AU - Lavigne, Rob

AU - Willis, Christine L

AU - Simpson, Thomas J

AU - Crosby, John

AU - Winn, Peter J

AU - Thomas, Christopher M

AU - Crump, Matthew P

PY - 2013/11

Y1 - 2013/11

N2 - 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.

AB - 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.

U2 - 10.1038/nchembio.1342

DO - 10.1038/nchembio.1342

M3 - Article

VL - 9

SP - 685

EP - 692

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 11

ER -