Screening of novel drug candidates in terestrial actinomycetes by using chemical and genomic tools

Terrestrial actinomycetes are an important source to discovery novel bioactive compounds. In this study, the previously isolated and identified rhizosphere Streptomyces strains were screened to explore the bioactive natural product capacity by using genomics and metabolomics approaches. The six Streptomyces strains (AA50, AS41, BA2, BS40, CA17 and CAH29) were cultivated in three modified culture media and metabolites were extracted by using different organic solvents. The antimicrobial activity was determined against to pathogen bacteria and C. albicans. The microbial organic extracts had high antibacterial activities against to all tested microbes. The highest antimicrobial activity in terms of high zone diameter and wide spectrum was obtained from culture extracts of GYM medium for all organisms. Metabolic profiling was performed by a non-targeted LC-MS/MS approach. Dereplication and tentative identification of natural products were evaluated for common chemical properties and their associated pathways. Significant bioactive natural products such as lyngbyatoxin A, actinomycin D, enterocin, alteramide B, malyngamide K and bouillonamide B were determined. The genome of Streptomyces sp. BA2 was prospected in search of biosynthetic gene clusters including polyketide synthase (PKS), nonribosomal peptide synthetase (NPRS), terpene, ectoin, indole, lantibiotics, and siderophores. It has been determined the considerable diversity of natural product biosynthetic gene clusters in its genome. More importantly, according to the glycogenomics study, an unknown glycosylated compound associated with a PKS-II butyrolactone gene cluster was established through chemical and genomic analyses.