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

Abstract

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.

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

“…The new dithiolopyrrolone antibiotic PR11 showed moderate to strong activity against all Gram‐positive bacteria, filamentous fungi and yeasts tested, but no activity against Gram‐negative bacteria. Similar results were observed with other known dithiolopyrrolones produced by our strain (Lamari et al ; Merrouche et al , , ).…”

“…Our previous studies showed that the antibacterial and antifungal activities of the dithiolopyrrolones are related to their variable acyl groups (Merrouche et al , , ). The new dithiolopyrrolone antibiotic PR11 showed moderate to strong activity against all Gram‐positive bacteria, filamentous fungi and yeasts tested, but no activity against Gram‐negative bacteria.…”

“…Likewise, the addition of sorbic acid (5 9 10 À3 mol) allowed formation of four new dithiolopyrrolone derivatives: crotonylpyrrothine, sorbyl-pyrrothine, 2-hexonyl-pyrrothine and 2-methyl-3-pentenylpyrrothine ( Fig. 1) (Merrouche et al 2011); while cinnamic acid addition (5 9 10 À3 mol) permitted the production of benzoyl-pyrrothine (Merrouche et al 2019) (Fig. 1).…”

Actinobacteria Derived from Algerian Ecosystems as a Prominent Source of Antimicrobial Molecules

“…Very recently, the same authors have reported on the new benzoyl-pyrrothine dithiolopyrrolone (14), obtained after the supplementation of cinnamic acid into the culture medium of S. algeriensis NRRL B-24137. In the antibacterial evaluation, Listeria monocytogenes resulted in the most sensitive to the treatment with this pure metabolite (MIC = 4 µg/mL corresponding to 13.8 µM) [84].…”

“…Compound 47 emerged as the most active in the series, mainly on Gram-positive bacteria and fungi (MICs in the range 1-50 µg/mL corresponding to 4.6-230 µM). [24,81] Valerylpyrrothine (6), Isovalerylpyrrothine (7), Formylpyrrothine (8), Aureothricin (9) antibacterial and antifungal Saccharothrix algeriensis NRRL B-24137, fully sequenced strain Saharan soil [82] Crotonyl-pyrrothine (10), Sorbyl-pyrrothine (11), 2-Hexenyl-pyrrothine (12), 2-Methyl-3-pentenyl-pyrrothine (13) antibacterial and antifungal Saccharothrix algeriensis NRRL B-24137 Saharan soil [83] Benzoyl-pyrrothine dithiolopyrrolone (14) antibacterial, antifungal Saccharothrix algeriensis NRRL B-24137 palm grove soil (Southern Algeria) [84] Mutactimycin PR (15) Toumatia et al [110] and, recently, Djinni et al [111] isolated novel strains producing actinomycin D (49) and showed that genus Streptomyces isolated from Saharan soil of Ain amenas (Streptomyces sp. IA1) and Beni Abbes-Bechar (Streptomyces sp.…”