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

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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; Ploskon, 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 journalArticle

Harvard

Haines, AS, Dong, X, Song, Z, Farmer, R, Williams, C, Hothersall, J, Ploskon, 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

Vancouver

Haines AS, Dong X, Song Z, Farmer R, Williams C, Hothersall J et al. A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis. Nature Chemical Biology. 2013 Nov;9(11):685-692. https://doi.org/10.1038/nchembio.1342

Author

Haines, Anthony S. ; Dong, Xu ; Song, Zhongshu ; Farmer, Rohit ; Williams, Christopher ; Hothersall, Joanne ; Ploskon, 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{3ee2d8dc8b9a4e24bb37490a1347015f,
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.",
keywords = "PSEUDOMONAS-FLUORESCENS NCIMB-10586, CYANOBACTERIUM LYNGBYA-MAJUSCULA, BIOSYNTHESIS GENE-CLUSTER, NMR-SPECTROSCOPY, NATURAL-PRODUCT, ANTIBIOTIC MUPIROCIN, BACILLUS-SUBTILIS, DIPOLAR COUPLINGS, COELICOLOR A3(2), CURACIN-A",
author = "Haines, {Anthony S.} and Xu Dong and Zhongshu Song and Rohit Farmer and Christopher Williams and Joanne Hothersall and Eliza Ploskon 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 = "11",
doi = "10.1038/nchembio.1342",
language = "English",
volume = "9",
pages = "685--692",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Springer Nature",
number = "11",

}

RIS - suitable for import to EndNote

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 - Ploskon, 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.

KW - PSEUDOMONAS-FLUORESCENS NCIMB-10586

KW - CYANOBACTERIUM LYNGBYA-MAJUSCULA

KW - BIOSYNTHESIS GENE-CLUSTER

KW - NMR-SPECTROSCOPY

KW - NATURAL-PRODUCT

KW - ANTIBIOTIC MUPIROCIN

KW - BACILLUS-SUBTILIS

KW - DIPOLAR COUPLINGS

KW - COELICOLOR A3(2)

KW - CURACIN-A

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 -