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PBP-A from\n                    <jats:italic>Thermosynechococcus elongatus<\/jats:italic>\n                    belongs to a cyanobacterial family of enzymes sharing close structural and phylogenetic proximity to class A \u03b2-lactamases. With the long-term aim of converting PBP-A into a \u03b2-lactamase by directed evolution, we simulated what may happen when an organism like\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    acquires such a new PBP and observed growth defect associated with the enzyme activity. To further explore the molecular origins of this harmful effect, we decided to characterize deeper the activity of PBP-A both in vitro and in vivo. We found that PBP-A is an enzyme endowed with\n                    <jats:sc>dd<\/jats:sc>\n                    -carboxypeptidase and\n                    <jats:sc>dd<\/jats:sc>\n                    -endopeptidase activities, featuring high specificity towards muropeptides amidated on the\n                    <jats:sc>d<\/jats:sc>\n                    -iso-glutamyl residue. We also show that a low promiscuous activity on non-amidated peptidoglycan deteriorates\n                    <jats:italic>E. coli\u2019s<\/jats:italic>\n                    envelope, which is much higher under acidic conditions where substrate discrimination is mitigated. Besides expanding our knowledge of the biochemical activity of PBP-A, this work also highlights that promiscuity may depend on environmental conditions and how it may hinder rather than promote enzyme evolution in nature or in the laboratory.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-64806-x","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:07:48Z","timestamp":1718669268000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PBP-A, a cyanobacterial dd-peptidase with high specificity for amidated muropeptides, exhibits pH-dependent promiscuous activity harmful to Escherichia coli"],"prefix":"10.1038","volume":"14","author":[{"given":"Gol Mohammad","family":"Dorrazehi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Winkle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Desmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Stroobant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Tanriver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Degand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Evrard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Desguin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Morsomme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Biboy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Mitusi\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"G\u00f3ra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Vollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Soumillion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"64806_CR1","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1128\/mmbr.67.4.593-656.2003","volume":"67","author":"H Nikaido","year":"2003","unstructured":"Nikaido, H. 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