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

Research output: Contribution to journalArticleResearchpeer review

Authors

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

Research Organisations

External Research Organisations

  • University of Bristol
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Details

Original languageEnglish
Pages (from-to)6777-6780
Number of pages4
JournalChemical communications
Volume52
Issue number41
Publication statusPublished - 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.

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Cite this

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, Vol. 52, No. 41, 01.01.2016, p. 6777-6780.

Research output: Contribution to journalArticleResearchpeer 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, vol. 52, no. 41, pp. 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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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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AU - Bonsch, B.

AU - Belt, V.

AU - Bartel, C.

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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.

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