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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (10): 737-746.DOI: 10.5246/jcps.2017.10.083

• Original articles • Previous Articles     Next Articles

Discovery of thiazostatin siderphores from Streptomyces sp. HMU0027 with a genomic DNA-based PCR assay targeting nonribosomal peptide synthetase

Fawang Liu, Mengjie Zhou, Jing Jin, Xiaoyan Yang, Yingtao Zhang, Ming Ma, Donghui Yang*   

  1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-07-07 Revised:2017-09-04 Online:2017-10-31 Published:2017-09-15
  • Contact: Tel.: +86-010-82801559, E-mail: ydhui@bjmu.edu.cn
  • Supported by:
    The National Natural Science Foundation of China (Grant No. 81573326, Grant No. 81673332).

Abstract:

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 carried 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 (17).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.

Key words: Genome mining, Nonribosomal peptide synthetase, Siderophore, Strain prioritization, Thiazostation

CLC Number: 

Supporting: