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NRPS substrate promiscuity leads to more potent antitubercular sansanmycin analogues
Yunying Xie1, Qiang Cai, Hao Ren
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing, People's Republic of China.
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).
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