Jump to main content
Jump to site search

Issue 8, 2016
Previous Article Next Article

Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis

Author affiliations

Abstract

Substrate salvage or recycling is common and important for primary metabolism in cells but is rare in secondary metabolism. Herein we report flavoenzyme CrmK-mediated shunt product recycling in the biosynthesis of caerulomycin A (CRM A 1), a 2,2′-bipyridine-containing natural product that is under development as a potent novel immunosuppressive agent. We demonstrated that the alcohol oxidase CrmK, belonging to the family of bicovalent FAD-binding flavoproteins, catalyzed the conversion of an alcohol into a carboxylate via an aldehyde. The CrmK-mediated reactions were not en route to 1 biosynthesis but played an unexpectedly important role by recycling shunt products back to the main pathway of 1. Crystal structures and site-directed mutagenesis studies uncovered key residues for FAD-binding, substrate binding and catalytic activities, enabling the proposal for the CrmK catalytic mechanism. This study provides the first biochemical and structural evidence for flavoenzyme-mediated substrate recycling in secondary metabolism.

Graphical abstract: Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis

Back to tab navigation

Supplementary files

Publication details

The article was received on 19 Feb 2016, accepted on 11 Apr 2016 and first published on 13 Apr 2016


Article type: Edge Article
DOI: 10.1039/C6SC00771F
Citation: Chem. Sci., 2016,7, 4867-4874
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Flavoenzyme CrmK-mediated substrate recycling in caerulomycin biosynthesis

    Y. Zhu, M. Picard, Q. Zhang, J. Barma, X. M. Després, X. Mei, L. Zhang, J. Duvignaud, M. Couture, W. Zhu, R. Shi and C. Zhang, Chem. Sci., 2016, 7, 4867
    DOI: 10.1039/C6SC00771F

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements