Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Katja M. Fisch
  • Walid Bakeer
  • Ahmed A. Yakasai
  • Zhongshu Song
  • Jennifer Pedrick
  • Zahida Wasil
  • Andrew M. Bailey
  • Colin M. Lazarus
  • Thomas J. Simpson
  • Russell J. Cox

Externe Organisationen

  • University of Bristol
  • University of Beni Suef
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Seiten (von - bis)16635-16641
Seitenumfang7
FachzeitschriftJournal of the American Chemical Society
Jahrgang133
Ausgabenummer41
PublikationsstatusVeröffentlicht - 19 Okt. 2011
Extern publiziertJa

Abstract

The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.

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Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. / Fisch, Katja M.; Bakeer, Walid; Yakasai, Ahmed A. et al.
in: Journal of the American Chemical Society, Jahrgang 133, Nr. 41, 19.10.2011, S. 16635-16641.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Fisch, KM, Bakeer, W, Yakasai, AA, Song, Z, Pedrick, J, Wasil, Z, Bailey, AM, Lazarus, CM, Simpson, TJ & Cox, RJ 2011, 'Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite', Journal of the American Chemical Society, Jg. 133, Nr. 41, S. 16635-16641. https://doi.org/10.1021/ja206914q
Fisch, K. M., Bakeer, W., Yakasai, A. A., Song, Z., Pedrick, J., Wasil, Z., Bailey, A. M., Lazarus, C. M., Simpson, T. J., & Cox, R. J. (2011). Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. Journal of the American Chemical Society, 133(41), 16635-16641. https://doi.org/10.1021/ja206914q
Fisch KM, Bakeer W, Yakasai AA, Song Z, Pedrick J, Wasil Z et al. Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. Journal of the American Chemical Society. 2011 Okt 19;133(41):16635-16641. doi: 10.1021/ja206914q
Fisch, Katja M. ; Bakeer, Walid ; Yakasai, Ahmed A. et al. / Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. in: Journal of the American Chemical Society. 2011 ; Jahrgang 133, Nr. 41. S. 16635-16641.
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AU - Bakeer, Walid

AU - Yakasai, Ahmed A.

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AU - Pedrick, Jennifer

AU - Wasil, Zahida

AU - Bailey, Andrew M.

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AU - Simpson, Thomas J.

AU - Cox, Russell J.

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