Exploiting Substrate Diversity of NRPS Led to the Generation of New Sansanmycin Analogs

Abstract

Further exploration of substrate diversity of the sansanmycin biosynthetic pathway using available halogen- and methyl-phenylalanines led to the generation of diverse sansanmycin derivatives, either at the single C- or N-terminus alone or at both C- and N-termini. The structures of all of these derivatives were determined by MS/MS spectra, and amongst them, the structures of [2-Cl-Phe]-sansanmycin H (1) and [2-Cl-Phe]-sansanmycin A (2) were further identified by NMR. Both the C-terminal derivative 1 and the N-terminal derivative 2 were assayed for their antibacterial activities, and compound 1 exhibited moderate activity against P. aeruginosa and ΔtolC mutant E. coli.