Isolation, Characterization and Chemical Synthesis of Large Spectrum Antimicrobial Cyclic Dipeptide (l-leu-l-pro) from Streptomyces misionensis V16R3Y1 Bacteria Extracts. A Novel 1H NMR Metabolomic Approach

Abstract

Streptomyces is the most frequently described genus of Actinomycetes, a producer of biologically active secondary metabolites. Indeed, the Streptomyces species produces about 70% of antibiotics and 60% of antifungal molecules used in agriculture. Our study was carried out with the goal of isolating and identifying antimicrobial secondary metabolites from <i>Streptomyces misionensis</i>V16R3Y1 isolated from the date palm rhizosphere (southern Tunisia). This strain presented a broad range of antifungal activity against <i>Fusarium</i> <i>oxysporum</i>, <i>Aspergillus</i> <i>fl</i><i>avus</i>, <i>Penicillium</i> <i>expansum</i>, <i>Aspergillus</i> <i>niger</i>, <i>Candida albicans</i>, <i>Candida</i> <i>metapsilosis</i>, and <i>Candida</i> <i>parapsilosis</i> and antibacterial activity against human pathogenic bacteria, including <i>Escherichia</i> <i>fergusonii</i>, <i>Staphylococcus aureus</i>, <i>Salmonella enterica</i>, <i>Enterococcus faecalis</i>, <i>Bacillus cereus</i> and <i>Pseudomonas aeruginosa</i>. The purification procedure entailed ethyl acetate extract, silica gel column, and thin layer chromatography. Based on 1H NMR metabolomic procedure application, also supported by the GC-MS analysis, cyclic dipeptide (l-Leucyl-l-Proline) was identified as the major compound in the bioactive fraction. In order to confirm the identity of the active compound and to have a large quantity thereof, a chemical synthesis of the cyclic dipeptide was performed. The synthetic compound was obtained with a very good yield (50%) and presented almost the same effect compared to the extracted fraction. This study indicates for the first time that <i>Streptomyces</i> <i>misionensis</i> V16R3Y1 exhibits a broad spectrum of antimicrobial activities, produced cyclic dipeptide (l-Leucyl-l-Proline) and might have potential use as a natural agent for pharmaceutical and agri-food applications.