title: NRPS substrate promiscuity leads to more potent antitubercular sansanmycin analogues.
abstract: Sansanmycins, members of the uridyl peptide antibiotics, are assembled by nonribosomal peptide synthetases (NRPSs), the substrate promiscuity of which results in the diversity of products. Further exploration of the NRPSs' substrate promiscuity by reinvestigating sansanmycin producer strain led to the isolation and structural elucidation of eight new uridyl peptides, sansanmycins H-O (1-8). Among them, sansanmycin L, containing a 6-OH-bicyclic residue and Phe3 first found at the position AA3, exhibited activity against M. tuberculosis H37Rv with an MIC value of 2 μg/mL, 8-fold more potent than that of the major compound, sansanmycin A (MIC = 16 μg/mL).
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, People's Republic of China.
authors: Yunying
authors: Y
authors: Xie
authors: Qiang
authors: Q
authors: Cai
authors: Hao
authors: H
authors: Ren
authors: Lifei
authors: L
authors: Wang
authors: Hongzhang
authors: H
authors: Xu
authors: Bin
authors: B
authors: Hong
authors: Linzhuan
authors: L
authors: Wu
authors: Ruxian
authors: R
authors: Chen
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010453:Peptide Synthases / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry*; D013379:Substrate Specificity; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D009842:Oligopeptides; C519865:sansanmycin; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; D014529:Uridine