Metabologenomic approach to discover aromatic polyketides, angucycline antimicrobial compounds produced by alkaliphilic <i>Streptomyces</i>

Streptomyces spp. is renowned for their capacity to produce structurally diverse secondary metabolites with potent bioactivities, including antimicrobial, antitumor, and antioxidant properties. In the present study, an alkaliphilic strain, designated as Streptomyces S9, was isolated and taxonomically characterised through multilocus sequence analysis (MLSA) using Streptomyces-specific primers. Extracted metabolites exhibited antimicrobial activity against Fusarium sp., Aspergillus sp., Corynespora sp., Bacillus sp., Staphylococcus aureus, Pseudomonas sp., and E. coli. Genomic DNA from strain S9 was subjected to PCR-based screening to detect biosynthetic gene clusters (BGCs) including nonribosomal peptide synthetase (NRPS), type I and type II polyketide synthase (PKS I and PKS II), and monooxygenase genes involved in the synthesis of natural products. Targeted amplification revealed the presence of PKS II and monooxygenase gene fragments, indicating its genetic potential to biosynthesise aromatic polyketides. Bioactive secondary metabolites were extracted from the culture supernatant, fractionated using preparative thin-layer chromatography (TLC), and subsequently analysed using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Bioactivity-guided fractionation identified two active fractions (AA2 and AA3) with bactericidal and fungicidal activity. LC-HRMS/MS analysis tentatively indicated two high-molecular-weight metabolites with [M + H]+ ion peaks at m/z 1355 and 1342, whose fragmentation patterns are analogous to glycosylated angucycline-type scaffolds, pending full structural confirmation by NMR spectroscopy.