A new dithiolopyrrolone antibiotic triggered by a long fermentation of Saccharothrix algeriensis NRRL B-24137 in sorbic acid-amended medium.

Saccharothrix algeriensis NRRL B-24137 is an actinobacterium isolated from Algerian Saharan soil. It produces bioactive compounds belonging to the dithiolopyrrolone class of antibiotics, which are characterized by the possession of a unique pyrrolinonodithiole nucleus. Dithiolopyrrolones are known for their strong antibacterial and antifungal activities. This class of antibiotics generated great interest after the discovery of their anticancer properties. In this study, an antibiotic named PR11, produced after a long bacterial fermentation (11 days) in sorbic acid-containing culture broth, was characterized as a new dithiolopyrrolone derivative. After HPLC analysis and purification, the chemical structure of this antibiotic was determined by 1 H- and 13 C-nuclear magnetic resonance, mass and UV-visible data. PR11 was thus characterized as an iso-hexanoyl-pyrrothine, a novel dithiolopyrrolone derivative. The minimum inhibitory concentrations of the new induced antibiotic were determined against several pathogenic micro-organisms. A moderate to strong activity was noted against all Gram-positive bacteria, filamentous fungi and yeasts tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Given the strong activities of dithiolopyrrolones against diverse prokaryotic and eukaryotic micro-organisms including potent selective-anticancer activity, the discovery of new-related derivatives draw continuous attention for therapeutic research. Depending on nature and concentration of added precursor, Saccharothrix algeriensis NRRL B-24137 produce several dithiolopyrrolone coumpounds. In this study, sorbic acid addition combined to long fermentation duration was shown to induce the biosynthesis of a novel dithiolopyrrolone derivative. After purification and full spectroscopic and spectrometric study, the compound was characterized as iso-hexanoyl-pyrrothine. In the future investigation for novel dithiolopyrrolone discovery, fermentation duration should be regarded as a key parameter as well.

Effective biosynthesis of benzoyl-pyrrothine dithiolopyrrolone antibiotic by cinnamic acid-precursor addition in culture of Saccharothrix algeriensis NRRL B-24137.

Dithiolopyrrolone antibiotics, produced by several micro-organisms, are known for their strong antimicrobial and antitumor activities. Among of this micro-organisms, Saccharothrix algeriensis NRRL B-24137, a rare actinobacterium, has the ability to produce several dithiolopyrrolones derivatives depending on precursors added in the culture medium. After 10 days of strain fermentation on semi-synthetic medium supplemented with cinnamic acid and HPLC purification, biosynthesis of benzoyl-pyrrothine dithiolopyrrolone was evidenced through complete spectroscopic (UV-visible and 1H and 13C NMR) and spectrometric (electron impact mass spectrum) analyses. The pure molecule showed appreciable minimum inhibitory concentration values against several Gram-positive bacteria and filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Dithiolopyrrolone antibiotics, known for their strong antimicrobial activities, gained greater interest after the discovery of their antitumor properties. Depending on precursors added, Saccharothrix algeriensis NRRL B-24137 has the ability to produce several dithiolopyrrolones derivatives. Since biological activities of dithiolopyrrolones are related to their variable structure, discover of new natural analogues to be therapeutically explored remains a significant framework of research. In this study, a new dithiolopyrrolone derivative was purified from the fermentation broth of S. algeriensis NRRL B-24137. This new antibiotic, characterized as benzoyl-pyrrothine dithiolopyrrolone, was induced by adding cinnamic acid, as precursor, to a semi-synthetic medium.