New Dithiolopyrrolone Antibiotics from Saccharothrix sp. SA 233. II. Physicochemical Properties and Structure Elucidation.

Lamari, Lynda; Zitouni, Abdelghani; Dob, Tahar; Sabaou, Nasserdine; Lebrihi, Ahmed; Germain, Pierre; Seguin, Elisabeth; Tillequin, François

doi:10.7164/antibiotics.55.702

Cited by 41 publications

(63 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Up to date, many bioactive secondary metabolites have been reported from cultures of Saccharothrix . These include for instance, tetrazomine [6], mutactimycin [7], and dithiolopyrroloe antibiotics [8]. These metabolites are characterised by diverse chemical structures and may be suitable because of their wide range of activity in agriculture to control fungal diseases in cultivated plants and domestic animals.…”

Section: Introductionmentioning

confidence: 99%

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T

Wang

Huang

Kang

et al. 2010

Journal of Biomedicine and Biotechnology

View full text Add to dashboard Cite

Strain Hhs.015T (Saccharothrix yanglingensis sp. nov.), an antagonistic endophytic Saccharothrix actinomycete isolated from roots of cucumber plants, exhibited a broad antimicrobial spectrum in vitro and was active as a biocontrol against plant diseases in field trials. The SSY medium was used for production of antimicrobial metabolites by strain Hhs.015T. However, this medium is too expensive for large-scale production. In this study, an alternative culture medium, based on agricultural waste products (e.g., apple pomace), was optimized. The results showed that the alternative medium contained 15 g apple pomace, 4 g rapeseed meal, 0.1 g KH2PO4, and 0.6 g MgSO4·7H2O in 1 L distilled water. This medium reduced the material costs by 91.5% compared to SSY medium. Response surface methodology (RSM) was used to investigate the influence of environmental variables on production of compounds of antimicrobial metabolites. The optimal conditions achieved were initial pH 7.0, medium volume of 90 mL in 250 mL flasks, rotary speed of 100 rpm, temperature 25°C, and inoculation volume of 15.8%. The antimicrobial activity was increased by 20% by optimizing the environmental parameters. The results obtained allow an efficient production of components with antimicrobial activity by strain Hhs.015T on a large scale at low costs.

show abstract

Section: Introductionmentioning

confidence: 99%

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T

Wang

Huang

Kang

et al. 2010

Journal of Biomedicine and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Other members of the dithiolopyrrolone class include aureothricin (1), the n-propionyl homolog of thiolutin, and a variety of xenorhabdins (4) with a longer acyl chain replacing the acetyl moiety of thiolutin and holomycin. Thiolutin and holomycin have been reported to display bacteriostatic activity against both Gram-positive and Gram-negative bacteria (5,6). Although the exact mechanism of action has not been determined, they appear to inhibit RNA synthesis and are active against rifamycin-resistant strains (7,8).…”

mentioning

confidence: 99%

Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus

Ли

Walsh

2010

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

Streptomyces clavuligerus, an industrially important producer of clavulanate as well as cephem antibiotics, also produces the N-acylated dithiolopyrrolone antibiotic holomycin, a reported inhibitor of RNA synthesis. The genome sequence of S. clavuligerus ATCC 27064 was examined for a potential biosynthetic gene cluster, assuming that holomycin arises from some derivative of an L-Cys-L-Cys dipeptide that has undergone eight-electron oxidation, fused five-five ring formation, and decarboxylation. ORFs 3483-3492 comprise a candidate cluster, with a predicted acyltransferase, a stand-alone nonribosomal peptide synthetase (NRPS) module, and four flavin-dependent oxidoreductases. Deletions of ORF3488, the NRPS module, and ORF3489, a phosphopantothenoylcysteine decarboxylase homolog, abolished holomycin production both in wild type and in a holomycin-overproducing mutant. Heterologous expression and purification of ORF3488 allowed demonstration of L-Cys-AMP formation and subsequent covalent tethering of Cys to the phosphopantetheinyl arm of the thiolation domain of this NRPS protein. Purified ORF3483 shows acyltransferase activity, converting holothin to holomycin and longer acylated homologs as the last step in antibiotic assembly.acylation | nonribosomal peptide synthetase

show abstract

“…Most recently, thiolutin, iso -butyropyrrothine and three new DTPs were isolated from the culture broth of Saccharothrix SA 233, a rare Actinomycetales present in the soils of palm groves from southern Algeria. 12,13 Among the new compounds from the Saccharothrix strain are two containing the unusual and potentially highly electrophilic α,β-unsaturated tigloyl and 3-methyl-2-butenoyl groups.…”

Section: Structures and Isolationmentioning

confidence: 99%

Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics

et al. 2014

View full text Add to dashboard Cite

Dithiolopyrrolone (DTP) group antibiotics were first isolated in the early half of the 20th century, but only recently has research been reawakened by insights gained from the synthesis and biosynthesis of this structurally intriguing class of molecules. DTPs are characterized by an electronically unique bicyclic structure, which contains a compact disulfide bridge between two ene-thiols. Points of diversity within the compound class occur outside of the bicyclic core, at the two amide nitrogens. Such modifications distinguish three of the most well studied members of the class, holomycin, thiolutin, and aureothricin; the DTP core has also more recently been identified in the marine antibiotic thiomarinol, in which it is linked to a marinolic acid moiety, analog of the FDA-approved topical antibiotic Bactroban® (GlaxoSmithKline). Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activity against many Gram-positive and Gram-negative bacteria, as well as strains of Mycobacterium tuberculosis. Additionally, they have been shown to exhibit potent and selective anti-cancer activity. Despite this promising profile, there is still much unknown about the mechanisms of action for DTPs. Early reports suggested that they inhibit yeast growth at the level of transcription and that this effect is largely responsible for their distinctive microbial static properties; a similar mechanism is supported in bacteria. Elucidation of biosynthetic pathways for holomycin in Streptomyces clavuligerus and Yersinia ruckeri and thiomarinol in Alteromonas rava sp. nov. SANK 73390, have contributed evidence suggesting that multiple mechanisms may be operative in the activity of these compounds. This review will comprehensively cover the history and development of dithiolopyrrolones with particular emphasis on the biosynthesis, synthesis, biological activity and mechanism of action.

show abstract

New Dithiolopyrrolone Antibiotics from Saccharothrix sp. SA 233. II. Physicochemical Properties and Structure Elucidation.

Cited by 41 publications

References 0 publications

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T

Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus

Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics

Contact Info

Product

Resources

About

New Dithiolopyrrolone Antibiotics from Saccharothrix sp. SA 233. II. Physicochemical Properties and Structure Elucidation.

Cited by 41 publications

References 0 publications

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015T

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015T

Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus

Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics

Contact Info

Product

Resources

About

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T

Optimization of the Fermentation Process of Actinomycete Strain Hhs.015^T