Awakening the Secondary Metabolite Pathways of Promicromonospora kermanensis Using Physicochemical and Biological Elicitors.

The drug discovery rate is dramatically decreasing due to the rediscovery of known compounds. Genome mining approaches have revealed that a large portion of the actinobacterial genome that encodes bioactive metabolites is cryptic and not expressed under standard lab conditions. In the present study, we aimed to induce antibiotic encoding biosynthetic genes in a member of Micrococcales as a new species of Promicromonospora, Promicromonospora kermanensis, by chemical and biological elicitors as it was considered to produce numerous valuable bioactive metabolites based on the whole genome results. Induction has been done via chemical (antibiotics, histone deacetylase inhibitors (HDAIs), rare earth elements (REEs), fatty acid synthesis inhibitors, and extreme pH changes) and biological elicitors (live and dead Gram-positive and negative bacteria). The results showed that valproic acid (as HDAIs), DMSO, lanthanum chloride (as REE), triclosan (as fatty acid synthesis inhibitors), alkaline pH, and supernatant of Pseudomonas aeruginosa UTMC 1404 culture could act as stimuli to provoke antibacterial synthetic pathways in Promicromonospora kermanensis DSM 45485. Moreover, it was revealed that eliciting agents in cell filtrated of P. aeruginosa culture is resistant to detergent, acidic, and basic condition and have amphipathic nature. The inducing effect of alkaline pH on metabolite induction of Actinobacteria was first reported in this study. In the follow-up studies, the induced antibacterial producing clusters can be subjected to the characterization, and the implemented approach in this study can be used for metabolites induction in other selected species.