In silico Screening of Biosynthetic Traits Driving Biotechnological Utility of Coagulase Negative, Food-Associated Staphylococcus Strains

Coagulase-negative staphylococci (CoNS) are increasingly recognized for their functional diversity and potential biotechnological value in food systems yet concerns persist regarding their safety and genomic plasticity. This study conducted a comprehensive comparative genomic assessment of seven food-associated species (‘7 CoNS’) to clarify their metabolic capabilities, biosynthetic potential, and biosafety attributes. Genomes were retrieved from NCBI, and pan-genome, orthologous clustering, subsystem classification, and phylogenomic analyses were performed using web-based tools (BV-BRC, KBase, OrthoVenn3, TYGS, and antiSMASH). The ‘7 CoNS’ collectively exhibited a conserved genetic backbone comprising 1,203 core functions and over 1,300 core gene families. Ortholog analyses identified 2,979 clusters, including 1,467 single-copy clusters, with species-specific patterns of unique and expanded gene families. Subsystem profiling revealed consistent distributions of metabolic, cellular, and stress-response functions, along with the presence of intrinsic tolerance determinants but no major transferable virulence genes. Biosynthetic gene cluster mining uncovered widespread siderophore and polyketide synthase clusters, with species-restricted clusters for metabolites such as ET-743, thailanstatin A, micrococcin P1, surfactin-like molecules, and marinacarbolines, highlighting distinct chemotypic niches. Conserved metabolic biomarkers, including key dehydrogenases, synthases, decarboxylases, and stress-response enzymes, further underscores the functional robustness of these taxa. Collectively, genomic evidence indicates evolutionary coherence, strong biotechnological potential, and low pathogenic risk among these food-associated CoNS strains. However, intrinsic antimicrobial resistance elements necessitate rigorous strain-level screening, as in silico predictions cannot confirm gene expression, enzyme activity, or metabolite production. This study provides an integrated genomic framework to support the safe, effective, and informed application of CoNS in fermentation and biotechnology. • Pan-genome analysis across 7 CoNS species revealed over 1,200 core functions • Metabolites in 7 CoNS BGCs include thailanstatin A, micrococcin P1 marinacarbolines • No major transferable virulence genes were detected in any of the 7 CoNS genome • Species-specific pathways across 7 CoNS include conserved metabolic biomarkers noted • Conserved stress-response genes linked to strong fermentation robustness were identified