Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases

Stephen F. Haydock; Jesús F. Aparicio; István Molnár; Torsten Schwecke; Lake Ee Khaw; Ariane König; Andrew F.A. Marsden; Ian S. Galloway; James Staunton; Peter F. Leadlay

doi:10.1016/0014-5793(95)01119-Y

Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases

Stephen F. Haydock
, Jesús F. Aparicio
, István Molnár
, Torsten Schwecke
, Lake Ee Khaw
, Ariane König
, Andrew F.A. Marsden
, Ian S. Galloway
, James Staunton
, Peter F. Leadlay^*

^*Corresponding author for this work

Not published at VTT

University of Cambridge

Research output: Contribution to journal › Article › Scientific › peer-review

216 Citations (Scopus)

Abstract

The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.

Original language	English
Pages (from-to)	246-248
Journal	FEBS Letters
Volume	374
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(95)01119-Y
Publication status	Published - 30 Oct 1995
MoE publication type	A1 Journal article-refereed

Funding

Acknowledgements': We thank the Wellcome Trust, the Biotechnology and Biological Research Council, and Pfizer Inc., Groton, USA for financial support, the Spanish Ministry of Education for a fellowship (to J.F.A) and the Medical Research Council for a training fellowship (to S.F.H.). We also thank Dr Z. Derewenda for kindly supplying the co-ordinates of the E. coli MCAT, and Dr H.A.I. McArthur and one of the referees for their helpful comments on the ms.

Keywords

Acyltransferase
Fatty acid synthase
Polyketide synthase
Sequence homology
Structural motif

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10.1016/0014-5793(95)01119-Y

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Haydock, S. F., Aparicio, J. F., Molnár, I., Schwecke, T., Khaw, L. E., König, A., Marsden, A. F. A., Galloway, I. S., Staunton, J., & Leadlay, P. F. (1995). Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases. FEBS Letters, 374(2), 246-248. https://doi.org/10.1016/0014-5793(95)01119-Y

@article{b55b31a57ded46618e03b146dfc5c243,

title = "Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases",

abstract = "The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.",

keywords = "Acyltransferase, Fatty acid synthase, Polyketide synthase, Sequence homology, Structural motif",

author = "Haydock, \{Stephen F.\} and Aparicio, \{Jes{\'u}s F.\} and Istv{\'a}n Moln{\'a}r and Torsten Schwecke and Khaw, \{Lake Ee\} and Ariane K{\"o}nig and Marsden, \{Andrew F.A.\} and Galloway, \{Ian S.\} and James Staunton and Leadlay, \{Peter F.\}",

note = "Funding Information: Acknowledgements': We thank the Wellcome Trust, the Biotechnology and Biological Research Council, and Pfizer Inc., Groton, USA for financial support, the Spanish Ministry of Education for a fellowship (to J.F.A) and the Medical Research Council for a training fellowship (to S.F.H.). We also thank Dr Z. Derewenda for kindly supplying the co-ordinates of the E. coli MCAT, and Dr H.A.I. McArthur and one of the referees for their helpful comments on the ms.",

year = "1995",

month = oct,

day = "30",

doi = "10.1016/0014-5793(95)01119-Y",

language = "English",

volume = "374",

pages = "246--248",

journal = "FEBS Letters",

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Haydock, SF, Aparicio, JF, Molnár, I, Schwecke, T, Khaw, LE, König, A, Marsden, AFA, Galloway, IS, Staunton, J & Leadlay, PF 1995, 'Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases', FEBS Letters, vol. 374, no. 2, pp. 246-248. https://doi.org/10.1016/0014-5793(95)01119-Y

Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases. / Haydock, Stephen F.; Aparicio, Jesús F.; Molnár, István et al.
In: FEBS Letters, Vol. 374, No. 2, 30.10.1995, p. 246-248.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases

AU - Haydock, Stephen F.

AU - Aparicio, Jesús F.

AU - Molnár, István

AU - Schwecke, Torsten

AU - Khaw, Lake Ee

AU - König, Ariane

AU - Marsden, Andrew F.A.

AU - Galloway, Ian S.

AU - Staunton, James

AU - Leadlay, Peter F.

N1 - Funding Information: Acknowledgements': We thank the Wellcome Trust, the Biotechnology and Biological Research Council, and Pfizer Inc., Groton, USA for financial support, the Spanish Ministry of Education for a fellowship (to J.F.A) and the Medical Research Council for a training fellowship (to S.F.H.). We also thank Dr Z. Derewenda for kindly supplying the co-ordinates of the E. coli MCAT, and Dr H.A.I. McArthur and one of the referees for their helpful comments on the ms.

PY - 1995/10/30

Y1 - 1995/10/30

N2 - The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.

AB - The amino acid sequences of a large number of polyketide synthase domains that catalyse the transacylation of either methylmalonyl-CoA or malonyl-CoA onto acyl carrier protein (ACP) have been compared. Regions were identified in which the acyltransferase sequences diverged according to whether they were specific for malonyl-CoA or methylmalonyl-CoA. These differences are sufficiently clear to allow unambiguous assignment of newly-sequenced acyltransferase domains in modular polyketide synthases. Comparison with the recently-determined structure of the malonyltransferase from Escherichia coli fatty acid synthase showed that the divergent region thus identified lies near the acyltransferase active site, though not close enough to make direct contact with bound substrate.

KW - Acyltransferase

KW - Fatty acid synthase

KW - Polyketide synthase

KW - Sequence homology

KW - Structural motif

UR - https://www.scopus.com/pages/publications/0028841535

U2 - 10.1016/0014-5793(95)01119-Y

DO - 10.1016/0014-5793(95)01119-Y

M3 - Article

C2 - 7589545

AN - SCOPUS:0028841535

SN - 0014-5793

VL - 374

SP - 246

EP - 248

JO - FEBS Letters

JF - FEBS Letters

IS - 2

ER -

Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases

Abstract

Funding

Keywords

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