Genome mining guided discovery and identification of nystatin and toyocamycin in Streptomyces hygrospinosus var. beijingensis

Abstract:

[Objective] We aimed to discover and identify the uncharacterized active components of Agricultural Antibiotic 120 by comprehensive analysis of genome sequence and secondary metabolites of Streptomyces hygroscopicus var. beijingensis (Bacteria, which produced Agricultural Antibiotic 120).[Methods] The genome sequence of wild-type strain was analyzed by antiSMASH for the sake of identifying possible biosynthetic gene clusters of nystatin and toyocamycin. HPLC, LC-MS and Q-TOF were used to analyze the secondary metabolites of wild-type strains, using chemical standards as control. Biosynthetic gene cluster (BGC) deletion mutants were constructed, and the fermentation products were analyzed.[Results] Biosynthetic BGCs of nystatin and toyocamycin were identified, and these two compounds were proved to be another two bioactive ingredients of Agricultural Antibiotic 120, besides the known anisomycin and tetramycin.[Conclusion]] The multiple BGC deletion mutant deducted the effect of compounds with high abundance and could serve as a good material to mine more natural compounds originally produced by WT strain. Moreover, correspondence analysis of genome sequence and metabolite profile was an effective method to identify compounds encoded by the silent biosynthetic gene clusters hidden in the genome.