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In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha\/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of\n                    <jats:italic>estX<\/jats:italic>\n                    is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the\n                    <jats:italic>estX<\/jats:italic>\n                    gene, predominantly pathogenic species like\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ,\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    , and\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the\n                    <jats:italic>estX<\/jats:italic>\n                    gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue.\n                  <\/jats:p>","DOI":"10.1038\/s42003-024-06473-2","type":"journal-article","created":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T13:02:02Z","timestamp":1719666122000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The global distribution of the macrolide esterase EstX from the alpha\/beta hydrolase superfamily"],"prefix":"10.1038","volume":"7","author":[{"given":"Jiafu","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-3828","authenticated-orcid":false,"given":"Yongqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-0372","authenticated-orcid":false,"given":"Tao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"6473_CR1","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/nrd3267","volume":"9","author":"B Hamad","year":"2010","unstructured":"Hamad, B. 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