Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • B. Bonsch
  • V. Belt
  • C. Bartel
  • N. Duensing
  • M. Koziol
  • C. M. Lazarus
  • A. M. Bailey
  • T. J. Simpson
  • R. J. Cox

Organisationseinheiten

Externe Organisationen

  • University of Bristol
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Details

OriginalspracheEnglisch
Seiten (von - bis)6777-6780
Seitenumfang4
FachzeitschriftChemical communications
Jahrgang52
Ausgabenummer41
PublikationsstatusVeröffentlicht - 1 Jan. 2016

Abstract

A gene cluster responsible for the biosynthesis of squalestatin S1 (SQS1, 1) was identified by full genome sequencing of two SQS1-producing ascomycetes: Phoma sp. C2932 and unidentified fungus MF5453. A transformation protocol was established and a subsequent knockout of one PKS gene from the cluster led to loss of SQS1 production and enhanced concentration of an SQS1 precursor. An acyltransferase gene from the cluster was expressed in E. coli and the expressed protein MfM4 shown to be responsible for loading acyl groups from CoA onto the squalestatin core as the final step of biosynthesis. MfM4 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins.

ASJC Scopus Sachgebiete

Zitieren

Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues. / Bonsch, B.; Belt, V.; Bartel, C. et al.
in: Chemical communications, Jahrgang 52, Nr. 41, 01.01.2016, S. 6777-6780.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Bonsch, B, Belt, V, Bartel, C, Duensing, N, Koziol, M, Lazarus, CM, Bailey, AM, Simpson, TJ & Cox, RJ 2016, 'Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues', Chemical communications, Jg. 52, Nr. 41, S. 6777-6780. https://doi.org/10.1039/c6cc02130a
Bonsch, B., Belt, V., Bartel, C., Duensing, N., Koziol, M., Lazarus, C. M., Bailey, A. M., Simpson, T. J., & Cox, R. J. (2016). Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues. Chemical communications, 52(41), 6777-6780. https://doi.org/10.1039/c6cc02130a
Bonsch B, Belt V, Bartel C, Duensing N, Koziol M, Lazarus CM et al. Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues. Chemical communications. 2016 Jan 1;52(41):6777-6780. doi: 10.1039/c6cc02130a
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title = "Identification of genes encoding squalestatin S1 biosynthesis and: In vitro production of new squalestatin analogues",
abstract = "A gene cluster responsible for the biosynthesis of squalestatin S1 (SQS1, 1) was identified by full genome sequencing of two SQS1-producing ascomycetes: Phoma sp. C2932 and unidentified fungus MF5453. A transformation protocol was established and a subsequent knockout of one PKS gene from the cluster led to loss of SQS1 production and enhanced concentration of an SQS1 precursor. An acyltransferase gene from the cluster was expressed in E. coli and the expressed protein MfM4 shown to be responsible for loading acyl groups from CoA onto the squalestatin core as the final step of biosynthesis. MfM4 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins.",
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note = "Funding information: We thank EPSRC (EP/F066104/1), Leibniz Universitat Hannover and DFG (INST 187/621) for funding LCMS instruments. CB Thanks the MINAS programme of Lower Saxony for funding. We thank the University of Bristol Genomics facility for Illumina genome sequencing.",
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T2 - In vitro production of new squalestatin analogues

AU - Bonsch, B.

AU - Belt, V.

AU - Bartel, C.

AU - Duensing, N.

AU - Koziol, M.

AU - Lazarus, C. M.

AU - Bailey, A. M.

AU - Simpson, T. J.

AU - Cox, R. J.

N1 - Funding information: We thank EPSRC (EP/F066104/1), Leibniz Universitat Hannover and DFG (INST 187/621) for funding LCMS instruments. CB Thanks the MINAS programme of Lower Saxony for funding. We thank the University of Bristol Genomics facility for Illumina genome sequencing.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - A gene cluster responsible for the biosynthesis of squalestatin S1 (SQS1, 1) was identified by full genome sequencing of two SQS1-producing ascomycetes: Phoma sp. C2932 and unidentified fungus MF5453. A transformation protocol was established and a subsequent knockout of one PKS gene from the cluster led to loss of SQS1 production and enhanced concentration of an SQS1 precursor. An acyltransferase gene from the cluster was expressed in E. coli and the expressed protein MfM4 shown to be responsible for loading acyl groups from CoA onto the squalestatin core as the final step of biosynthesis. MfM4 appears to have a broad substrate selectivity for its acyl CoA substrate, allowing the in vitro synthesis of novel squalestatins.

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