Enhancement and Identification of Microbial Secondary Metabolites

Screening for microbial secondary metabolites (SMs) has attracted the attention of the scientific community since 1940s. In fact, since the discovery of penicillin, intensive researches have been conducted worldwide in order to detect and identify novel microbial secondary metabolites. As a result, the discovery of novel SMs has been decreased significantly by using traditional experiments. Therefore, searching for new techniques to discover novel SMs was one of the most priority objectives. However, the development and advances of omics-based techniques such as metabolomics and genomics have revealed the potential of discovering novel SMs which were coded in the microorganisms’ DNA but not expressed in the lab media or might be produced in undetectable amount by detecting the biosynthesis gene clusters (BGCs) that are associated with the biosynthesis of secondary metabolites. Nowadays, the development and integration of gene editing tools such as CRISPR-Cas9 in metabolomics provide a successful platform for the identification and detection of known and novel SMs and also to increase the production of SMs

Ru(CO)(3)Cl(Glycinate) (CORM-3): A Carbon Monoxide-Releasing Molecule with Broad-Spectrum Antimicrobial and Photosensitive Activities Against Respiration and Cation Transport in Escherichia coli

Aims: Carbon monoxide (CO) delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas. The metal carbonyl Ru(CO)3Cl(glycinate) (CORM-3) is a novel, potent antimicrobial agent. Here, we established its mode of action. Results: CORM-3 inhibits respiration in several bacterial and yeast pathogens. In anoxic Escherichia coli suspensions, CORM-3 first stimulates, then inhibits respiration, but much higher concentrations of CORM-3 than of a classic protonophore are required for stimulation. Proton translocation measurements (H+/O quotients, i.e., H+ extrusion on pulsing anaerobic cells with O2) show that respiratory stimulation cannot be attributed to true ‘‘uncoupling,’’ that is, dissipation of the protonmotive force, or to direct stimulation of oxidase activity. Our data are consistent with CORM-3 facilitating the electrogenic transmembrane movement of K+ (or Na+), causing a stimulation of respiration and H+ pumping to compensate for the transient drop in membrane potential (DJ). The effects on respiration are not mimicked by CO gas or control Ru compounds that do not release CO. Inhibition of respiration and loss of bacterial viability elicited by CORM-3 are reversible by white light, unambiguously identifying heme-containing oxidase(s) as target(s). Innovation: This is the most complete study to date of the antimicrobial action of a CO-RM. Noteworthy are the demonstration of respiratory stimulation, electrogenic ion transport, and photosensitive activity, establishing terminal oxidases and ion transport as primary targets. Conclusion: CORM-3 has multifaceted effects: increased membrane permeability, inhibition of terminal oxidases, and perhaps other unidentified mechanisms underlie its effectiveness in tackling microbial pathogenesis