Nonribosomal antibacterial peptides isolated from Streptomyces agglomeratus 5-1-3 in the Qinghai-Tibet Plateau

Microbial Cell Factories

Research

Yehong Guo¹  Kan Jiang¹  Guangxiu Liu²  Ximing Chen²  Wei Zhang² 

[1]College of Agronomy, State Key Laboratory of Aridland Crop Science, Gansu Agricultural University, 730070, Lanzhou, Gansu, China

[2]Key Laboratory of Desert and Desertification, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, 730030, Lanzhou, Gansu, China

[3]Key Laboratory of Extreme Environmental Microbial Resources and Engineering, 730030, Lanzhou, Gansu, China

关键词: S. agglomeratus;    Antibacterial;    Echinomycin;    Nonribosomal peptides;    MRSA;   

DOI  :  10.1186/s12934-023-02018-0

 received in 2022-08-07, accepted in 2023-01-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNew antibiotics are urgently needed in clinical treatment of superdrug-resistant bacteria. Nonribosomal peptides (NRPs) are a major source of antibiotics because they exhibit structural diversity, and unique antibacterial mechanisms and resistance. Analysis of gene clusters of S. agglomeratus 5-1-3 showed that Clusters 3, 6, 12, 21, and 28 were used to synthesize NRPs. Here, we examined secondary metabolites of S. agglomeratus 5-1-3 isolated from soils in the Qinghai-Tibet Plateau, China, for NRPs with antibacterial activity.ResultsWe isolated a total of 36 Streptomyces strains with distinct colony morphological characteristics from 7 soil samples. We screened 8 Streptomyces strains resistant to methicillin-resistant Staphylococcus aureus (MRSA). We then selected S. agglomeratus 5-1-3 for further study based on results of an antibacterial activity test. Here, we isolated three compounds from S. agglomeratus 5-1-3 and characterized their properties. The crude extract was extracted with ethyl acetate and purified with column chromatography and semipreparative high-performance liquid chromatography (HPLC). We characterized the three compounds using NMR analyses as echinomycin (1), 5,7,4ʹ-trihydroxy-3.3′,5′-trimethoxy flavone (2), and 2,6,2′, 6′-tetramethoxy-4,4-bis(2,3-epoxy-1-hydroxypropyl)-biphenyl (3). We tested the antibacterial activity of pure compounds from strain 5-1-3 with the Oxford cup method. NRP echinomycin (1) showed excellent anti-MRSA activity with a minimum inhibitory concentration (MIC) of 2.0 μg/mL. Meanwhile, MIC of compound 2 and 3 was 128.0 μg/mL for both. In addition, 203 mg of echinomycin was isolated from 10 L of the crude extract broth of strain 5-1-3.ConclusionIn this study, S. agglomeratus 5-1-3 with strong resistance to MRSA was isolated from the soils in the Qinghai-Tibet Plateau. Strain 5-1-3 had a high yield of echinomycin (1) an NRP with a MIC of 2 μg/mL against MRSA. We propose that echinomycin derived from S. agglomeratus 5-1-3 may be a potent antibacterial agent for pharmaceutical use.

【 授权许可】

CC BY   
© The Author(s) 2023

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