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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,12]]},"abstract":"<jats:p>\n                    Aromatic polyketides are renowned for their wide-ranging pharmaceutical activities. Their structural diversity is mainly produced via modification of limited types of basic frameworks. In this study, we characterized the biosynthesis of a unique basic aromatic framework, phenyldimethylanthrone (PDA) found in (+)\/(\u2212)-anthrabenzoxocinones (ABXs) and fasamycin (FAS). Its biosynthesis employs a methyltransferase (Abx\n                    <jats:sub>(+)<\/jats:sub>\n                    M\/Abx\n                    <jats:sub>(\u2212)<\/jats:sub>\n                    M\/FasT) and an unusual TcmI-like aromatase\/cyclase (ARO\/CYC, Abx\n                    <jats:sub>(+)<\/jats:sub>\n                    D\/Abx\n                    <jats:sub>(\u2212)<\/jats:sub>\n                    D\/FasL) as well as a nonessential helper ARO\/CYC (Abx\n                    <jats:sub>(+)<\/jats:sub>\n                    C\/Abx\n                    <jats:sub>(\u2212)<\/jats:sub>\n                    C\/FasD) to catalyze the aromatization\/cyclization of polyketide chain, leading to the formation of all four aromatic rings of the PDA framework, including the C9 to C14 ring and a rare angular benzene ring. Biochemical and structural analysis of Abx\n                    <jats:sub>(+)<\/jats:sub>\n                    D reveals a unique loop region, giving rise to its distinct acyl carrier protein-dependent specificity compared to other conventional TcmI-type ARO\/CYCs, all of which impose on free molecules. Mutagenic analysis discloses critical residues of Abx\n                    <jats:sub>(+)<\/jats:sub>\n                    D for its catalytic activity and indicates that the size and shape of its interior pocket determine the orientation of aromatization\/cyclization. This study unveils the tetracyclic and non-TcmN type C9 to C14 ARO\/CYC, significantly expanding our cognition of ARO\/CYCs and the biosynthesis of aromatic polyketide framework.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2321722121","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T13:47:26Z","timestamp":1709732846000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":9,"title":["An unusual aromatase\/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0589-7202","authenticated-orcid":false,"given":"Kai","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China"},{"name":"Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China"},{"name":"Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjun","family":"Li","sequence":"additional","affiliation":[{"name":"Abiochem Biotechnology Co. 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