Quinone exchanges in the gut microbiota
Résumé
Isoprenoid quinones are hydrophobic molecules shuttling electrons in the respiratory chains of most living organisms. Menaquinone (MK) or Vitamin K is the most commonly found isoprenoid quinone in bacteria and archaea and mainly found in anaerobic respiration. The biosynthesis of MK relies on two multi-steps pathways, “Men” or “Futalosine”, that mostly do not co-exist in genomes. Interestingly, some bacterial species in the human gut microbiota encode MK-dependent respiratory proteins but possess only an incomplete Men pathway . A possibility is that these species may respire with MK synthesized from MK precursors cross-fed by donor species. This phenomenon was proposed in the literature but it has never been characterized. The first goal of this project is to annotate the Men pathway and some MK-dependent proteins in all bacterial species of the human gut microbiota. For this, we used bioinformatic analyses, which highlighted the importance of genomes displaying a partial Men pathway, including for bacteria beneficial to human health like Bifidobacteria. In parallel, the experimental part of this study showed that this detected and truncated pathway can be used to produce quinones by supplementing the medium with a natural precursor within the Men pathway (DHNA) or by performing a co-culture with a donor candidate like Escherichia coli. Finally, in a more global approach, a method is developed to quantify the overall quinone composition of the gut microbiota, that we called the quinome. As quinones are very diverse within the tree of life, we hypothesize that the quinome may differ between balanced and dysbiotic microbiota, this last state being known to seriously impact human health.