The FlxABCD-HdrABC Proteins Correspond to a Novel NADH dehydrogenase/heterodisulfide Reductase Widespread in Anaerobic Bacteria and Involved in Ethanol Metabolism in Desulfovibrio Vulgaris Hildenborough

Environ Microbiol. 2015 Jul;17(7):2288-305. doi: 10.1111/1462-2920.12689. Epub 2015 Jan 27.


Flavin-based electron bifurcation (FBEB) is an important mechanism for the energy metabolism of anaerobes. A new family of NADH dehydrogenases, the flavin oxidoreductase (FlxABCD, previously called FloxABCD), was proposed to perform FBEB in sulphate-reducing organisms coupled with heterodisulfide reductase (HdrABC). We found that the hdrABC-flxABCD gene cluster is widespread among anaerobic bacteria, pointing to a general and important role in their bioenergetics. In this work, we studied FlxABCD of Desulfovibrio vulgaris Hildenborough. The hdr-flx genes are part of the same transcriptional unit and are increased in transcription during growth in ethanol-sulfate, and to a less extent during pyruvate fermentation. Two mutant strains were generated: one where expression of the hdr-flx genes was interrupted and another lacking the flxA gene. Both strains were unable to grow with ethanol-sulfate, whereas growth was restored in a flxA-complemented strain. The mutant strains also produced very reduced amounts of ethanol compared with the wild type during pyruvate fermentation. Our results show that in D. vulgaris, the FlxABCD-HdrABC proteins are essential for NADH oxidation during growth on ethanol, probably involving a FBEB mechanism that leads to reduction of ferredoxin and the small protein DsrC, while in fermentation they operate in reverse, reducing NAD(+) for ethanol production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Desulfovibrio vulgaris / enzymology*
  • Desulfovibrio vulgaris / genetics
  • Electrons
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Ethanol / metabolism*
  • FMN Reductase / metabolism*
  • Ferredoxins / metabolism
  • NAD / metabolism
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Pyruvic Acid / metabolism
  • Sulfates / metabolism


  • Ferredoxins
  • Sulfates
  • NAD
  • Ethanol
  • Pyruvic Acid
  • Oxidoreductases
  • heterodisulfide reductase
  • FMN Reductase
  • NADH Dehydrogenase