Nonribosomal peptides （NRPs） represent a large family of natural products with great diversities of chemical structures and biological activities. The peptide backbones of NRPs are synthesized by nonribosomal peptid...Nonribosomal peptides （NRPs） represent a large family of natural products with great diversities of chemical structures and biological activities. The peptide backbones of NRPs are synthesized by nonribosomal peptide synthetases （NRPSs） that minimally consist of one adenylation （A） domain, one peptidyl carrier protein （PCP） and one condensation （C） domain. In this study, we carded out a PCR screening and identified 21 ＂positive＂ strains from 100 actinomycete strains with the degenerate primers designed from the conserved sequences of A domains of NRPSs. One of the 21 ＂positive＂ strains, Streptomyces sp. HMU0027, was selected for large-scale fermentation （9 L） based on HPLC analysis, and subsequent isolation and structural elucidation afforded seven NRPS-synthesized thiazostatin siderophore analogues （1-7）. Compound 1 was a new compound containing an unusual linkage between a phenolate siderophore and a sugar moiety. These results laid the foundation for further biosynthetic research of these thiazostatin analogues and highlighted the power of genome mining technologies based on biosynthetic knowledge in NRP discovery.展开更多
基金The National Natural Science Foundation of China(Grant No.81573326,Grant No.81673332)
文摘Nonribosomal peptides （NRPs） represent a large family of natural products with great diversities of chemical structures and biological activities. The peptide backbones of NRPs are synthesized by nonribosomal peptide synthetases （NRPSs） that minimally consist of one adenylation （A） domain, one peptidyl carrier protein （PCP） and one condensation （C） domain. In this study, we carded out a PCR screening and identified 21 ＂positive＂ strains from 100 actinomycete strains with the degenerate primers designed from the conserved sequences of A domains of NRPSs. One of the 21 ＂positive＂ strains, Streptomyces sp. HMU0027, was selected for large-scale fermentation （9 L） based on HPLC analysis, and subsequent isolation and structural elucidation afforded seven NRPS-synthesized thiazostatin siderophore analogues （1-7）. Compound 1 was a new compound containing an unusual linkage between a phenolate siderophore and a sugar moiety. These results laid the foundation for further biosynthetic research of these thiazostatin analogues and highlighted the power of genome mining technologies based on biosynthetic knowledge in NRP discovery.
