If bacteria are ranked by the number of commercially available antibiotics produced, Streptomyces would be number one by an overwhelming margin—producing more approved drugs than all other bacterial genera combined. Streptomyces is a group of filamentous, Gram-positive, soil-dwelling bacteria. Streptomyces species possess large (7–12 Mb) genomes, significantly larger than those of most other bacteria. Many species also carry large linear plasmids. The hallmark of Streptomyces genomics is the presence of numerous secondary metabolite biosynthetic gene clusters (BGCs), one of the most critical reasons for Streptomyces species having an exceptional capacity for antibiotics production. Each cluster contains a co-localized set of genes responsible for the biosynthesis, tailoring, regulation, resistance, and transport of a specific secondary metabolite. Major BGC types include polyketide synthase (PKS) clusters, non-ribosomal peptide synthase (NRPS) clusters, hybrid PKS-NRPS clusters, ribosomally synthesized and post-translationally modified peptide clusters, and terpene and siderophore clusters; and the most important classes and prototype examples of antibiotics produced include aminoglycosides (e.g., streptomycin, neomycin, kanamycin, tobramycin), polyketides (e.g., erythromycin, tetracycline, rifampicin), non-ribosomal peptides (e.g., vancomycin, teicoplanin, daptomycin), chloramphenicol, and β-lactam (cephamycins, clavulanic acid, thienamycin, imipenem). Most antibiotic-producing Streptomyces species encode self-resistance genes within or near the BGC, ensuring that antibiotic production does not harm the producing organism. Advancement of technologies, such as next-generation sequencing, robust bioinformatics tools, and artificial intelligence-based methods, could reveal the hidden or silent BGCs and enable genome mining, activation of silent pathways and discovery of entirely new antibiotics in Streptomyces that traditional methods would miss.
Tam et al. (Thu,) studied this question.