Supplementary file 1_The regulatory role of histidine kinase in modulating nucleoside metabolites in Streptomyces noursei CK-15.docx

Histidine kinase (HK), a vital component of the two-component system (TCS), regulates the synthesis of secondary metabolites and is integral to key processes related to the growth and environmental adaptation of Streptomyces. The SHK gene may govern the manufacture of the nucleoside-type secondary metabolites Toyocamycin and Wuyiencin. This study generated a histidine kinase overexpression mutant strain (S. noursei oSHK) exploiting ΔtoyG transcription data. This mutant strain was seen to suppress the growth of the CK-15 strain, resulting in a 25.94% reduction in Wuyiencin levels and a 17.64% decrease in Toyocamycin levels, while also decreasing spore formation and hyphal development rate. The SHK gene demonstrates reduced efficacy against bacteria and compromised nitrogen use. These findings suggest a detrimental regulatory influence of the SHK gene on strain viability and secondary metabolite synthesis in S. noursei CK-15, and this study provides theoretical justification for the modification of high-yielding Wuyiencin strains.