Abstract:Background Streptomyces from extreme cold environments represent significant candidate sources of novel bioactive natural products and play crucial roles in the discovery of new antibiotic lead compounds. Systematic studies on Streptomyces resources originating from Hoh Xil remain to be carried out.Objective To identify a strain of actinomycetes with broad-spectrum antimicrobial activity against multiple test strains isolated from the unique soil environment of Hoh Xil, and evaluate its potential for producing antimicrobial substances, aiming to provide core data to support the subsequent development and utilization of active metabolites.Methods The antimicrobial activity of strain 24-1644 fermentation broth against various pathogens including methicillin-resistant Staphylococcus aureus (MRSA) was determined by the Kirby-Bauer (K-B) disc diffusion assay. The stability of this strain under heat, acid/alkali, and UV irradiation was evaluated. The antiSMASH tool was employed for prediction and analysis of biosynthetic gene clusters (BGCs) in the strain genome. COG and KEGG databases were used for gene function annotation. The strain was preliminarily identified by morphological, physiological, and biochemical characterization, phylogenetic analyses based on 16S rRNA gene sequencing results and genome sequences, and DNA-DNA hybridization assay.Results The fermentation broth of strain 24-1644 exhibited significant inhibitory activity against S. aureus, Mycobacterium smegmatis, and MRSA, along with varying degrees of inhibition against Escherichia coli, drug-resistant E. coli, and Bacillus subtilis. The inhibitory activity remained stable within certain temperature and pH ranges but was sensitive to UV irradiation. The genome of strain 24-1644 harbored key biosynthetic gene clusters (BGCs) for polyketides, nonribosomal peptides, terpenoids, and other diverse BGCs. Among them, eight BGCs showed low structural similarity (15%-50%) to known clusters, while 16 exhibited <15% similarity, suggesting high potential for novel secondary metabolite production. The annotation in COG and KEGG databases revealed 4 082 and 2 978 genes, respectively, among which 1 730 (42.38%) and 1 680 (56.41%) were involved in metabolic processes. The morphological, physiological, and biochemical characterization, phylogenetic analyses based on 16S rRNA gene sequences and genome sequences, and DNA-DNA hybridization data suggested that strain 24-1644 was most closely related to Streptomyces durocortorensis yet genetically distinct.Conclusion Strain 24-1644 represents a potential novel Streptomyces resource closely related to S. durocortorensis, with its fermentation broth exhibiting broad-spectrum and stable antimicrobial activity. Genomic analysis reveals that the strain harbors key BGCs for polyketides, nonribribosomal peptides, and terpenoids, indicating substantial potential for secondary metabolite production. The strain is predicted to harbor numerous novel BGCs, demonstrating significant research value for developing new antimicrobial lead compounds.
