Reassessing the substrate specificities of the majorStaphylococcus aureuspeptidoglycan hydrolases lysostaphin and LytM

• DOI: 10.1101/2023.10.13.562287
• Publication Date: 2023-10-14T04:00:12Z
• Authors: Lina Antenucci; Salla Virtanen; Chandan Thapa; Minne Jartti; Ilona Pitkänen; Helena Tossavainen; Perttu Permi
• Keywords: Lysostaphin

Abstract Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth viability. Although the function several PG well-understood, function, regulation, mechanism characterized as lysostaphin-like endopeptidases have remained elusive. Many these M23 family members can hydrolyse glycyl-glycine peptide bonds show lytic activity against Staphylococcus aureus whose contains a pentaglycine bridge, but their exact substrate specificity hydrolysed are still vaguely determined. In this work, we employed NMR spectroscopy to study both bond cleavage bactericide lysostaphin S. hydrolase LytM. Yet, provide substrate-level evidence functional role enzymes. Indeed, our results that specificities structurally highly homologous enzymes similar, unlike observed earlier LytM prefer D-Ala-Gly cross-linked part mature peptidoglycan. However, while genuinely hydrolase, also act D-alanyl-glycine endopeptidase.