Genomic insights and biosynthetic gene cluster analysis of Streptomyces chrestomyceticus strain B5 showing antimicrobial activities.

UNLABELLED: Streptomyces bacteria are known for their different biological activities and enormous biosynthetic potential. Fungal pathogens, especially Candida auris, have emerged as clinically important pathogens involved in causing systemic infections and high mortality. Therefore, antimicrobial compounds effective against C. auris are needed to tackle infections caused by these multidrug-resistant yeast pathogens. A soil bacterium was isolated from soil in Delhi, India, exhibited broad-spectrum antimicrobial activities against various pathogenic bacteria, such as Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, and pathogenic fungi, including Candida albicans, Fusarium oxysporum, Aspergillus fumigatus, and Candida glabrata. It was subjected to whole-genome sequencing and resulted in a high-quality draft genome with a single contig of 9.61 Mb genome size and 72.1% GC content. Phylogenetic analysis and average nucleotide identity identified that the strain belongs to Streptomyces chrestomyceticus. The genome annotation predicted plant growth-promoting traits and stress-response genes. Genome mining revealed non-ribosomal peptide synthetase, polyketide synthase (PKS), and hybrid biosynthetic gene clusters (BGCs) synthesizing known and unknown metabolites. Most of the encoded compounds by the BGCs were reported for antibacterial and antitumor activities, and two BGCs were identified as antifungal clusters. A trans-acyltransferase polyketide synthase (transAT-PKS) cluster was identified with 27% and 19% similarity to cycloheximide and 9-methylstreptimidone clusters, respectively. The comparison of 9-methylstreptimidone and transAT-PKS cluster revealed differences in the organization of genes in closely related strains. The crude extract of S. chrestomyceticus B5 possessed strong antibacterial and antifungal activities. The bioassay-guided purification and LC-MS identified an antifungal compound (streptimidone derivative or isomer, molecular mass 293.1 Da), which specifically inhibited C. glabrata and C. auris. The transAT-PKS cluster might be responsible for encoding this streptimidone derivative or isomer.

IMPORTANCE: The study highlighted the biosynthetic potential of Streptomyces chrestomyceticus B5, which is a promising strain for producing various bioactive metabolites and is rich in biosynthetic gene clusters responsible for encoding multiple metabolites and producing an antifungal compound, a streptimidone derivative or isomer, active against drug-resistant Candida auris.