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

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Awakening the Secondary Metabolite Pathways of Promicromonospora kermanensis Using Physicochemical and Biological Elicitors Fatemeh Mohammadipanah 1

1

& Fatemeh Kermani & Fatemeh Salimi

2

Received: 2 April 2020 / Accepted: 22 June 2020/ # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract

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. Keywords Actinobacteria . Antibiotics . Bioactive secondary metabolites . Cryptic pathways . Elicitors . Promicromonospora kermanensis

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12010-02003361-3) contains supplementary material, which is available to authorized users.

* Fatemeh Mohammadipanah [email protected] Extended author information available on the last page of the article

Applied Biochemistry and Biotechnology

Introduction It is predicted that the antibiotic-resistant strains lead to 10 million deaths by 2050 and impose an economic cost of $100 trillion [1, 2]. Many antibiotics have been discovered from Actinobacteria as a rich source of natural compounds, and mining rare Actinobacteria are one of the most promising strategies to find new and structurally diverse microbial-derived compounds [3]. The time-consuming and labor-intensive process of purification and structure elucidation of isolated antibiotics and, in particular, the high percentage of the rediscovery of previously known c