Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity

Gut Microbes. 2018;9(5):437-451. doi: 10.1080/19490976.2018.1435244. Epub 2018 Jun 4.

Abstract

The discovery of enzymes responsible for previously unappreciated microbial metabolic pathways furthers our understanding of host-microbe and microbe-microbe interactions. We recently identified and characterized a new gut microbial glycyl radical enzyme (GRE) responsible for anaerobic metabolism of trans-4-hydroxy-l-proline (Hyp). Hyp dehydratase (HypD) catalyzes the removal of water from Hyp to generate Δ1-pyrroline-5-carboxylate (P5C). This enzyme is encoded in the genomes of a diverse set of gut anaerobes and is prevalent and abundant in healthy human stool metagenomes. Here, we discuss the roles HypD may play in different microbial metabolic pathways as well as the potential implications of this activity for colonization resistance and pathogenesis within the human gut. Finally, we present evidence of anaerobic Hyp metabolism in sediments through enrichment culturing of Hyp-degrading bacteria, highlighting the wide distribution of this pathway in anoxic environments beyond the human gut.

Keywords: 4-hydroxyproline; Clostridioides difficile; Stickland fermentation; amino acid metabolism; collagen; enrichment culturing; glycyl radical enzyme; gut microbiome; human 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 / enzymology*
  • Bacteria / genetics
  • Bacteria / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gastrointestinal Microbiome*
  • Gastrointestinal Tract / microbiology
  • Humans
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism*
  • Hydroxyproline / chemistry
  • Hydroxyproline / metabolism*
  • Metabolic Networks and Pathways
  • Metagenome
  • Microbiota
  • Phylogeny

Substances

  • Bacterial Proteins
  • Hydro-Lyases
  • Hydroxyproline

Grants and funding

This work was financially supported by Harvard University and a Pckard Fellowship for Science and Engineering (2013-39267). Y.H. is a fellowship recipient of NSERC Postgraduate sholarship-Doctoral Program. We thank the Simons Foundation, the National Science Foundation, the National Aeronautics and Space Administration, and the U.S. Department of Energy for providing financial support for the Microbial Diversity course. Y.H. is grateful to be funded by Abagail Salyers Scholarship Fund and Simons MD Scholarship to attend the Microbial Diversity course.