Antimicrobial DAAO-generated peptides
PI: Loredano Pollegioni and Giulia Murtas
Pollegioni et al., 2018. Human D-amino acid oxidase: structure, function, and regulation. Front Mol Biosci. 5:107. doi: 10.3389/fmolb.2018.00107.
Marcone et al., 2020. D-amino acids in foods. Appl Microbiol Biotechnol. 104:555-574. doi: 10.1007/s00253-019-10264-9.
Marcone et al., 2019. Antibacterial properties of D-amino acid oxidase: impact on the food industry. Front Microbiol. 10:2786. doi: 10.3389/fmicb.2019.02786.
Murtas et al., 2021. Antimicrobial D-amino acid oxidase-derived peptides specify gut microbiota. Cell Mol Life Sci. doi: 10.1007/s00018-020-03755-w.
Fondazione Cariplo (Grant 2018-2786)
Gabriella Tedeschi and Elisa Maffioli, University of Milan, Milan, IT
Eugenio Notomista and Valeria Cafaro, University of Naples Federico II, Naples, IT
Monica Abbondi, Fondazione Istituto Insubrico Ricerca per la Vita, Gerenzano, IT
Jean-Pierre Mothet, Université Paris-Saclay, CNRS, ENS Paris-Saclay, Gif-sur-Yvette, FR
During the last years, alterations in the composition of gut microbiota (the population of microorganisms that colonizes the human intestinal tract) have been associated with different human pathologies ranging from luminal, metabolic and allergic diseases to neurodevelopmental illnesses. Recently, the gut microbiota was unexpectedly shown to induce the expression of the flavoenzyme D-amino acid oxidase and its secretion by intestinal epithelial cells. DAAO in turn was proposed to control the microbiota homeostasis through the hydrogen peroxide generated by the oxidative deamination of D-amino acids, derived from diet or the microbial cell wall.
However, we propose an alternative mechanism in the DAAO-mediated selection of gut microbiota: we identified two putative antimicrobial peptides in the flavoenzyme’s primary structure. These peptides show antimicrobial activity on Gram-positive and Gram-negative bacteria. These peptides are also present in the gut.
Further studies performed in collaboration with a number of reserch groups, indicate that the proteolytic digestion of the secreted DAAO yields to the release of the antibacterial peptides which then affect the microbiota composition.