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During searching for new chemical entities regulating MDR\u2010 and XDR\u2010Mtb, chemical investigation of the black oil beetle gut bacterium\n                    <jats:italic>Micromonospora<\/jats:italic>\n                    sp. GR10 led to the discovery of eight new members of arenicolides along with the identification of arenicolide A (Ar\u2212A,\n                    <jats:bold>1<\/jats:bold>\n                    ), which was a previously reported macrolide with incomplete configuration. Genomic analysis of the bacterial strain GR10 revealed their putative biosynthetic pathway. Quantum mechanics\u2010based computation, chemical derivatizations, and bioinformatic analysis established the absolute stereochemistry of Ar\u2212A and arenicolides D\u2212K (Ar\u2212D\u2212K,\n                    <jats:bold>2<\/jats:bold>\n                    \u2013\n                    <jats:bold>9<\/jats:bold>\n                    ) completely for the first time. Biological studies of\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>9<\/jats:bold>\n                    revealed their antimicrobial activity against MDR and XDR strains of Mtb. Ar\u2212A had the most potent in vitro antimicrobial efficacy against MDR\u2010 and XDR\u2010Mtb. Mechanistically, Ar\u2212A induced ATP depletion and destabilized Mtb cell wall, thereby inhibiting growth. Notably, Ar\u2212A exerted a significant antimicrobial effect against Mtb in macrophages, was effective in the treatment of Mtb infections, and showed a synergistic effect with amikacin (AMK) in a mouse model of MDR\u2010Mtb lung infection. Collectively, our findings indicate Ar\u2212A to be a promising drug lead for drug\u2010resistant tuberculosis.\n                  <\/jats:p>","DOI":"10.1002\/anie.202412994","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T10:10:30Z","timestamp":1728900630000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Arenicolide Family Macrolides Provide a New Therapeutic Lead Combating Multidrug\u2010Resistant Tuberculosis"],"prefix":"10.1002","volume":"64","author":[{"given":"Sunghoon","family":"Hwang","sequence":"first","affiliation":[{"name":"Natural Products Research Institute College of Pharmacy Seoul National University  1 Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Eun","family":"Heo","sequence":"additional","affiliation":[{"name":"Division of Life Science Department of Bio &amp; Medical Big Data (BK21 Four Program) Research Institute of Life Science Gyeongsang National University  52828 Jinju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh Quang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Life Science Department of Bio &amp; 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Discovery and Department of Chemistry Yale University  West Haven 06516 CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungoo","family":"Park","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology Chonnam National University  61186 Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Joon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute College of Pharmacy Seoul National University  1 Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"},{"name":"MolGenBio Co., Ltd.  08826 Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"},{"name":"Department of Medical Science College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"},{"name":"Department of Medical Science College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungweon","family":"Ryoo","sequence":"additional","affiliation":[{"name":"Clinical Research Centre Masan National Tuberculosis Hospital  51755 Changwon-si Gyeongsangnam-do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Gyum","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Research Centre Masan National Tuberculosis Hospital  51755 Changwon-si Gyeongsangnam-do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Wood","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Laboratory Institute Pasteur Korea  13488 Seongnam-si Gyeonggi-do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjeong","family":"Woo","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Laboratory Institute Pasteur Korea  13488 Seongnam-si Gyeonggi-do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae\u2010Duk","family":"Kim","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute College of Pharmacy Seoul National University  1 Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"},{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences  1 Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungwha","family":"Paik","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"},{"name":"Department of Medical Science College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Kyeong","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Microbiology College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"},{"name":"Department of Medical Science College of Medicine Chungnam National University  35015 Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichan","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Life Science Department of Bio &amp; 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