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

Abstract

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 1H‐ and 13C‐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.

Structure of Potential Dithiolopyrrolone Antibiotics Detected from the DART-ToF-MS Spectra of Saccharothrix algeriensis Extract

“…However, all these isomers have been reported to be produced by S. algeriensis. 1,[24][25][26][27] As reported previously, some DTPs were detected by HPLC only after addition of some precursors to enhance their production. 1,[24][25][26][27] However, it is important to mention that, in the present work, all the detected DTPs were easily observed by DART-ToF-MS, without precursor feeding.…”

“…All the characterised eleven DTPs were already reported to be produced by S. algeriensis. 1,3,[24][25][26][27] It was established that the positive ionisation in DART ion source can occur through three possible mechanisms by interaction with the heated and excited metastable helium atoms, with no or little fragmentation. Generally, the main observed peak corresponds to a protonated adduct ion [M+H] + ; it results from protonation by interaction with atmospheric water molecules.…”

“…1 Seven other new DTP analogs: iso-valerylpyrrothine (h), 2-hex-onyl-pyrrothine (i), 2-methyl-3-pentenyl-pyrrothine (j), iso-hexanoyl-pyrrothine (k) (also named iso-pentyl-formylpyrrothine), propionyl-pyrrothine, crotonyl-pyrrothine, and sorbyl-pyrrothine were also obtained from S. algeriensis using the same technique. [24][25][26][27] The structures of these compounds are shown in Fig. 1.…”

Saccharothrix obliqua sp. nov., isolated from soil of Sichang Island, Thailand

“…Cyanogrisides I–J were isolated from Saccharothrix xinjiangensis [6]. Iso-hexanoyl-pyrrothine, a dithiolopyrrolone antibiotic, was isolated from Saccharothrix algeriensis NRRL B-24137 [7]. This compound showed potent antibacterial and antifungal activities.…”

Actinobacteria From Desert: Diversity and Biotechnological Applications

“…A4 and A5 also exhibited modest antifungal ability against filamentous fungi such as Ascochyta fabae , Aspergillus carbonarius , F. culmorum , Fusarium equiseti , M. ramannianus , and Penicillium expansum . By incorporating sorbic acid into its culture medium, S. algeriensis NRRL B-24137 produced five novel dithiolopyrrolone antibiotics: PR2, PR8, PR9, PR10, and PR11 ( Merrouche et al, 2011 , 2019 ). These five antibiotics showed antimicrobial activity against Gram-positive bacteria, filamentous fungi, and yeasts, including B. subtilis , B. coagulans , L. monocytogenes , M. luteus , S. aureus , A. carbonarius , F. oxysporum f.sp.…”