Muta-mycosynthesis of naphthalene analogs.
A mutasynthetic strategy is introduced for the mycosynthesis of naphthalene-based molecules (mutadalesols A-F) with directed substitution patterns and new frameworks by generating and using the ΔpksTL mutant strain of Daldinia eschscholzii. (±)-Mutadalesol A and its (+)-enantiomer are cytotoxic, and its (-)-enantiomer inhibits Toll-like receptor 5 (TLR5). The in-culture reactability of fungal oligoketide intermediates with 5-aminonaphthalen-1-ol (ANL) is demonstrated, shedding light on bioorthogonal accesses to unnatural molecule libraries valuable in drug discovery pipelines.
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Yuan
Y
Tian
‡School of Pharmacy, Nanjing Medical University, Nanjing, 210029, China.
Nan
N
Jiang
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Ai Hua
AH
Zhang
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Chao Jun
CJ
Chen
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Xin Zhao
XZ
Deng
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Wen Jing
WJ
Zhang
†Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Ren Xiang
RX
Tan
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry* / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D051198:Toll-Like Receptor 5 / Q000187:drug effects
D000970:Antineoplastic Agents; D009281:Naphthalenes; D051198:Toll-Like Receptor 5; C000600284:mutadalesol A