Computational genomic discovery of diverse gene clusters harbouring Fe-S flavoenzymes in anaerobic gut microbiota

Microb Genom. 2020 May;6(5):e000373. doi: 10.1099/mgen.0.000373. Epub 2020 May 12.


The gut contains an enormous diversity of simple as well as complex molecules from highly diverse food sources, together with host-secreted molecules. This presents a large metabolic opportunity for the gut microbiota, but little is known about how gut microbes are able to catabolize this large chemical diversity. Recently, Fe-S flavoenzymes were found to be key in the transformation of bile acids, catalysing the key step in the 7α-dehydroxylation pathway that allows gut bacteria to transform cholic acid into deoxycholic acid, an exclusively microbe-derived molecule with major implications for human health. While this enzyme family has also been implicated in a limited number of other catalytic transformations, little is known about the extent to which it is of more global importance in gut microbial metabolism. Here, we perform a large-scale computational genomic analysis to show that this enzyme superfamily has undergone a remarkable expansion in Clostridiales, and occurs throughout a diverse array of >1000 different families of putative metabolic gene clusters. Analysis of the enzyme content of these gene clusters suggests that they encode pathways with a wide range of predicted substrate classes, including saccharides, amino acids/peptides and lipids. Altogether, these results indicate a potentially important role of this protein superfamily in the human gut, and our dataset provides significant opportunities for the discovery of novel pathways that may have significant effects on human health.

Keywords: Clostridium; flavoenzymes; gene clusters; gut microbiota.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anaerobiosis
  • Bacteria / classification*
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cholic Acid / metabolism
  • Deoxycholic Acid / metabolism
  • Ferredoxin-NADP Reductase / genetics*
  • Ferredoxin-NADP Reductase / metabolism
  • Gastrointestinal Microbiome
  • Genomics / methods*
  • Humans
  • Multigene Family
  • Phylogeny


  • Bacterial Proteins
  • Deoxycholic Acid
  • Ferredoxin-NADP Reductase
  • Cholic Acid