Journal Article

Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota

2021

Overview

The flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.

• Publisher: Springer Nature B.V
• Subject: Amino acid oxidase / Amino acids / Antiinfectives and antibacterials / Antimicrobial agents / Antimicrobial peptides / Bacteria / Biodegradation / D-Amino acids / D-Amino-acid oxidase / Digestive system / Enantiomers / Enzymatic activity / Gastrointestinal tract / Goblet cells / Gram-negative bacteria / Gut microbiota / Homeostasis / Hydrogen peroxide / Intestinal microflora / Intestine / Lactobacilli / Microbiota / Mucosa / Peptides