Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires cooexpression with an enoyl reductase

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Laura M. Halo
  • James W. Marshall
  • Ahmed A. Yakasai
  • Zhongshu Song
  • Craig P. Butts
  • Matthew P. Crump
  • Mary Heneghan
  • Andrew M. Bailey
  • Thomas J. Simpson
  • Colin M. Lazarus
  • Russell J. Cox

External Research Organisations

  • University of Bristol
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Details

Original languageEnglish
Pages (from-to)585-594
Number of pages10
JournalCHEMBIOCHEM
Volume9
Issue number4
Publication statusPublished - 3 Mar 2008
Externally publishedYes

Abstract

The tenS gene encoding tenellin synthetase (TENS), a 4239-residue polyketide synthase nonribosomal-peptide synthetase (PKSNRPS) from Beauveria bassiana, was expressed in Aspergillus oryzae M-2-3. This led to the production of three new compounds, identified as acyl tetramic acids, and numerous minor metabolites. Consideration of the structures of these compounds indicates that the putative C-terminal thiolester reductase (R) domain does not act as a reductase, but appears to act as a Dieckmann cyclase (DKC). Expression of tenS in the absence of a trans-acting ER component encoded by orf3 led to errors in assembly of the polyketide component, giving clues to the mode of programming of highly reducing fungal PKS. Coexpression of tenS with orf3 from the linked gene cluster led to the production of a correctly elaborated polyketide. The NRPS adenylation domain possibly shows the first identified fungal signature sequences for tyrosine selectivity.

Keywords

    Beauveria, Biosynthesis, Fungi, Heterologous expression, Natural products

ASJC Scopus subject areas

Cite this

Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires cooexpression with an enoyl reductase. / Halo, Laura M.; Marshall, James W.; Yakasai, Ahmed A. et al.
In: CHEMBIOCHEM, Vol. 9, No. 4, 03.03.2008, p. 585-594.

Research output: Contribution to journalArticleResearchpeer review

Halo, LM, Marshall, JW, Yakasai, AA, Song, Z, Butts, CP, Crump, MP, Heneghan, M, Bailey, AM, Simpson, TJ, Lazarus, CM & Cox, RJ 2008, 'Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires cooexpression with an enoyl reductase', CHEMBIOCHEM, vol. 9, no. 4, pp. 585-594. https://doi.org/10.1002/cbic.200700390
Halo, L. M., Marshall, J. W., Yakasai, A. A., Song, Z., Butts, C. P., Crump, M. P., Heneghan, M., Bailey, A. M., Simpson, T. J., Lazarus, C. M., & Cox, R. J. (2008). Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires cooexpression with an enoyl reductase. CHEMBIOCHEM, 9(4), 585-594. https://doi.org/10.1002/cbic.200700390
Halo LM, Marshall JW, Yakasai AA, Song Z, Butts CP, Crump MP et al. Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires cooexpression with an enoyl reductase. CHEMBIOCHEM. 2008 Mar 3;9(4):585-594. doi: 10.1002/cbic.200700390
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abstract = "The tenS gene encoding tenellin synthetase (TENS), a 4239-residue polyketide synthase nonribosomal-peptide synthetase (PKSNRPS) from Beauveria bassiana, was expressed in Aspergillus oryzae M-2-3. This led to the production of three new compounds, identified as acyl tetramic acids, and numerous minor metabolites. Consideration of the structures of these compounds indicates that the putative C-terminal thiolester reductase (R) domain does not act as a reductase, but appears to act as a Dieckmann cyclase (DKC). Expression of tenS in the absence of a trans-acting ER component encoded by orf3 led to errors in assembly of the polyketide component, giving clues to the mode of programming of highly reducing fungal PKS. Coexpression of tenS with orf3 from the linked gene cluster led to the production of a correctly elaborated polyketide. The NRPS adenylation domain possibly shows the first identified fungal signature sequences for tyrosine selectivity.",
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AU - Marshall, James W.

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