Analysis of Secondary Metabolite Synthesis Potential of Streptomyces fradiae sf106 Based on the Whole Genome and Non-Target Metabolomics and Exploration of the Biosynthesis of Tylosin

Abstract

Streptomyces fradiae sf106 is a type of actinomycete that can produce abundant secondary metabolites, making it a natural cell factory for drug synthesis. In order to comprehensively understand the genomic profile of Streptomyces fradiae sf106 and its potential for producing secondary metabolites, a combination of several methods was used to perform whole-genome sequencing of sf106. The results showed that sf106 is most closely related to Streptomyces xinghaiensis S187; the average nucleotide identity and average amino acid identity of sf106 and S187 were more than 96%. The genome size of sf106 is approximately 7300 kb, the GC content is greater than 72%, and more than 6700 coding sequences (CDS) were identified. Analysis of mobile genetic elements revealed the presence of a large number of horizontally transferred genes in Streptomyces fradiae sf106, which contribute to microbial diversity. Through antiSMASH prediction, 22 secondary metabolite gene clusters were obtained, which had great potential to generate polyketide metabolites. By examining the data, it was found that the genes contained in cluster 9 were similar to those involved in tylosin synthesis. Non-targeted metabolome sequencing revealed that a total of 1855 identifiable metabolites were produced in the fermentation broth, and the majority of metabolites showed highly significant differences in mean relative abundance between the groups. The identified metabolites were compared against the KEGG compound database to obtain metabolite classifications, mainly including Biological Roles, Phytochemical Compounds, Lipids, and Pesticides. One-way ANOVA indicated that the relative concentration of tylosin differed significantly across all the growth periods, except for the late-logarithmic and stabilization stages. This study provides important basic information on the secondary metabolite research of sf106, which will help us to understand and apply Streptomyces fradiae sf106 more comprehensively.