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A global understanding of their evolution and sequence and functional diversity can therefore aid a wide set of different disciplines. Interestingly, \u03b2-lactamases have evolved multiple times from distinct evolutionary origins, with ancestries that reach back billions of years. It is therefore no surprise that these enzymes exhibit diverse structural features and enzymatic mechanisms. In this review, we provide a bird\u2019s eye view on the evolution of \u03b2-lactamases within the two enzyme superfamilies\u2014i.e. the penicillin-binding protein-like and metallo-\u03b2-lactamase superfamily\u2014through phylogenetics. We further discuss potential evolutionary origins of each \u03b2-lactamase class by highlighting signs of evolutionary connections in protein functions between \u03b2-lactamases and other enzymes, especially cases of enzyme promiscuity.<\/jats:p>","DOI":"10.1093\/protein\/gzab013","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T11:07:22Z","timestamp":1620558442000},"source":"Crossref","is-referenced-by-count":53,"title":["Evolution of \u03b2-lactamases and enzyme promiscuity"],"prefix":"10.1093","volume":"34","author":[{"given":"Christopher","family":"Fr\u00f6hlich","sequence":"first","affiliation":[{"name":"The Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, UiT The Arctic University of Norway, Troms\u00f8 9037, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Z","family":"Chen","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevan","family":"Gholipour","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse N","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Tokuriki","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"2021070812441225500_ref1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1586\/eri.13.21","volume":"11","author":"Abbott","year":"2013","journal-title":"Expert Rev. 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