Genome Mining Strategies to Unlock the Metabolic Potential of Streptomyces sp. VITGV100 (MCC 4961) for Next-Generation Antimicrobial Discovery

John Godwin Christopher^1*Dr. Veilumuthu Pattapulavar¹Dr. Saranyadevi S²Sathiyabama Ramanujam²Riyanka Shill¹Priyanka Velmurugan¹TAPAS GHATAK¹Dr. Sanjivkumar Muthusamy³Antony V Samrot⁴

• ¹VIT University, Vellore, India
• ²Karpagam Academy of Higher Education, Coimbatore, India
• ³Department of Microbiology, K.R. College of Arts & Science, K.R. Nagar, Kovilpatti, Tamil Nadu, India, Kovilpatti, India
• ⁴Melaka Manipal Medical College - Meleka Campus, Bukit Baru, Malaysia

Background The rising burden of antimicrobial resistance (AMR) necessitates new bioactive molecules that are both sustainable and therapeutically relevant. Endophytic actinomycetes, particularly Streptomyces, represent a valuable but underexplored source of secondary metabolites with pharmaceutical potential. Methods An endophytic strain, Streptomyces sp. VITGV100, was isolated from tomato stems and subjected to genome sequencing and antiSMASH analysis. A total of 35 compounds were predicted and their associated Biosynthetic gene clusters were identified, including non-ribosomal peptide synthetases, polyketide synthases, RiPPs, terpenes, and melanin. In silico pharmacokinetics (SwissADME), target prediction (SwissTargetPrediction, DisGeNET), and pathway enrichment (Reactome) were combined with molecular docking and dynamic simulations to prioritize drug-like metabolites. The antibacterial activity of crude extracts was experimentally evaluated against Escherichia coli and Staphylococcus aureus. Results In silico profiling revealed 11 compounds with favorable drug-like properties and no Lipinski violations. Target mapping implicated clinically relevant proteins such as carbonic anhydrase 2 (CA2), PARP1, and PPARA, associated with metabolic disorders, neurodegeneration, and cancer. Docking demonstrated strong binding affinities (–7.4 to –9.6 kcal/mol) for melanin, isorenieratene, and albaflavenone, with stable interactions involving Zn²⁺ coordination and hydrophobic contacts. PASS prediction suggested broad antineoplastic activity, complemented by moderate antibacterial potential. In vitro assays confirmed inhibitory zones of 15–20 mm against E. coli and S. aureus, supporting the computational predictions. Conclusion This integrative genome-to-function pipeline establishes Streptomyces sp. VITGV100 as a sustainable microbial cell factory for next-generation antimicrobials and multifunctional bioactives. The study highlights the value of combining genome mining, cheminformatics, and experimental validation to unlock cryptic biosynthetic pathways. Future work on metabolic engineering and CRISPR-based refactoring could enhance yields, advancing endophyte-derived Streptomyces as renewable platforms for antimicrobial and anticancer drug discovery.