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Adv."],"published-print":{"date-parts":[[2025,3,7]]},"abstract":"<jats:p>\n                    Non-tuberculous mycobacteria (NTM) is gaining clinical recognition as a recently emerging pulmonary pathogen.\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    complex (MAC), the most common NTM, is the cause of pulmonary MAC disease. Currently, the macrolide azithromycin (AZM) is the standard first-line antibiotic for treatment of the disease. However, the rise of drug-resistant MAC necessitates the development of alternative therapeutics. Here, we present a late-stage boron-mediated aglycon delivery strategy for selective modification of AZM, generating a library of potential anti-MAC drugs designated\n                    <jats:bold>KU01<\/jats:bold>\n                    to\n                    <jats:bold>KU13<\/jats:bold>\n                    . Screening of\n                    <jats:bold>KU01<\/jats:bold>\n                    to\n                    <jats:bold>KU13<\/jats:bold>\n                    revealed that\n                    <jats:bold>KU13<\/jats:bold>\n                    exhibited enhanced antimicrobial activity against wild-type and macrolide-resistant MAC compared to AZM. Cryo\u2013electron microscopy analysis indicated that the inserted tercyclic moiety of\n                    <jats:bold>KU13<\/jats:bold>\n                    formed a robust anchor on the bacterial ribosome, creating a binding pocket with base flipping of U2847, potentially bypassing the standard mechanism of macrolide resistance. These results position\n                    <jats:bold>KU13<\/jats:bold>\n                    as a promising lead for therapeutics against macrolide-resistant MAC.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt2352","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T13:58:51Z","timestamp":1741183131000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Creation of a macrolide antibiotic against non-tuberculous\n                    <i>Mycobacterium<\/i>\n                    using late-stage boron-mediated aglycon delivery"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9713-2128","authenticated-orcid":true,"given":"Yuka","family":"Isozaki","sequence":"first","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Makikawa","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7448-1729","authenticated-orcid":true,"given":"Daiki","family":"Nishihara","sequence":"additional","affiliation":[{"name":"Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5796-8331","authenticated-orcid":true,"given":"Maho","family":"Fujino","sequence":"additional","affiliation":[{"name":"Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan."},{"name":"The Advanced Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chigusa","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimasa","family":"Ishizaki","sequence":"additional","affiliation":[{"name":"Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1562-6685","authenticated-orcid":true,"given":"Masayuki","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-9140","authenticated-orcid":true,"given":"Takeshi","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan."},{"name":"The Advanced Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-9099","authenticated-orcid":true,"given":"Kazunobu","family":"Toshima","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-6648","authenticated-orcid":true,"given":"Daisuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, 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