A stoichiometric reaction scheme for Saccharothrix algeriensis growth and thiolutin production (original) (raw)
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Saccharothrix algeriensis, a new antibiotic producer: investigations on its secondary metabolism
The constant growth of the antibiotic world market leads to study rare actinomycete. Therefore, the bacterium Saccharothrix algeriensis which products new antibiotics of dithiolopyrrolone class is studied in liquid culture. The aim of this work is to better apprehend the mechanisms which govern the bacterial growth as well as the dithiolopyrrolones synthesis and to capitalize this knowledge in a general reactional scheme of the metabolism. The growth of Saccharothrix algeriensis was performed in a batch reactor, on a semisynthetic medium. The growth, the thiolutine (the main dithiolopyrrolone) and the carbon dioxide production and the substrates consumption were monitored. The influence of the substrate concentration on growth and on the production of dithiolopyrrolones was evaluated. It seems that diauxic growth occurs on amino acids then on glucose. The thiolutine synthesis would be induced by carbon substrates exhaustion and by ammonium ions deficiency. Glucose seems to exert a catabolite repression on the secondary metabolic activities of the cell.
Process Biochemistry, 2007
The influence of organic acids on growth and dithiolopyrrolone antibiotic production by Saccharothrix algeriensis NRRL B-24137 was studied. The production of dithiolopyrrolones depends upon the nature and concentration of the organic acids in the culture medium. Study of the nature of organic acids showed that the most effective organic acids for thiolutin specific production were maleic, 4-hydroxybenzoic, benzentetracarboxylic, pantothenic, pivalic
Investigations of Saccharothrix algeriensis growth on synthetic media
Journal of Bioscience and Bioengineering, 2008
Development of bacterial resistance to antibiotics has lead to investigations of rare bacteria, which produce new bioactive molecules. Saccharothrix algriensis has been isolated from the desert Maghreb. It produces dithiolopyrrolones, some of which were newly identified. In order to optimize and control production of dithiolopyrrolones, investigation regarding microorganism metabolism was required. Growth on semisynthetic medium containing 2 g ⋅l -1 of yeast extract was complicated because it was performed on several substrates. Moreover, because development of this bacterium on minimum medium was difficult, its composition was optimized by screening of different compounds led by yeast extract. Uracil added to the minimum medium allowed a maximum biomass production of 1.35 g ⋅l -1 compared to 0.32 g ⋅l -1 without uracil. Moreover, nonpolar amino acids and trace metal elements stimulated Saccharothrix algeriensis growth.
Process Biochemistry, 2018
The production of dithiolopyrrolones by Saccharothrix algeriensis was investigated after supplementing the culture medium with ethanol and/or 1-butanol. Optimized Optimal conditions for the addition of ethanol to the culture medium provided a maximal dithiolopyrrolone titer of about 200 mg⋅L-1 after 5 days of culture, roughly corresponding to a 600%-increase. The involvement of ethanol in enzyme-mediated reactive oxygen species generation, using diphenyleneiodonium, NAD(P)H oxidase inhibitor, was observed. Using NAD(P)H oxidase inhibitor (diphenyleneiodonium) or reactive oxygen species scavenger (para-aminobenzoic acid), we suppose that ethanol promotes the formation generation of reactive oxygen species in Saccharothrix algeriensis, which, in turn, act as elicitors for could induce biomass decline and dithiolopyrrolone overproduction. However, the underlying mechanisms remain to be elucidated. These results may be helpful for the optimization control of dithiolopyrrolone yields from Saccharothrix algeriensis cultures. and thus pave the way toward their large-scale production.
Journal of Applied Microbiology, 2006
To study the effect of sulfur-containing amino acids (L-cysteine, L-cystine, L-methionine and DL-ethionine) on the production of dithiolopyrrolone antibiotics by Saccharothrix algeriensis NRRL B-24137. Methods and Results: The production levels of dithiolopyrrolones were investigated by using high performance liquid chromatography in a chemically semisynthetic medium. The production of the studied antibiotics depends upon the nature, concentration and the time of addition of these sources in the culture medium. Both cysteine and cystine favoured the specific productions of dithiolopyrrolones; iso-butyryl-pyrrothine (ISP) by cysteine, however butanoylpyrrothine, senecioyl-pyrrothine and tigloyl-pyrrothine by cystine, when added initially to the culture medium. The maximum specific productions of dithiolopyrrolones were observed in the presence of 5 mmol l )1 cystine for thiolutin, 5 mmol l )1 cysteine for ISP, and 10 mmol l )1 cystine for others studied dithiolopyrrolones as shown in . The production of these antibiotics was decreased when the concentrations of cysteine and cystine were in excess. All dithiolopyrrolone specific productions were strongly inhibited by addition of methionine and ethionine, without inhibition of mycelial growth. Conclusions: Among all studied amino acids, cystine and cysteine can be used as supplements for improvement the production of dithiolopyrrolone antibiotics by S. algeriensis NRRL B-24137. Significance and Impact of the Study: Dithiolopyrrolone antibiotics have many important applications for employing them as medicaments, particularly in the treatment of human and animal cancers. In the present work, the influence of containing-sulfur amino acids on dithiolopyrrolone antibiotic productions was studied. The obtained results can be employed for the optimization of the culture medium for the dithiolopyrrolone productions in higher quantities.
Letters in Applied Microbiology, 2019
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.
FEMS Microbiology Letters, 2011
Dithiolopyrrolone antibiotics, produced by several microorganisms, are known for their strong antimicrobial activities. This class of antibiotics generated new interest after the discovery of their anticancer and antitumor properties. In this study, four new antibiotics were purified from the fermentation broth of Saccharothrix algeriensis NRRL B-24137 and characterized as dithiolopyrrolone derivatives. These new dithiolopyrrolone antibiotics were induced by adding sorbic acid, as precursor, at a concentration of 5 mM to the semi-synthetic medium. The analysis of the induced antibiotics was carried out by HPLC. The maximal production of the antibiotics PR2, PR8, PR9 and PR10 was 0.08 AE 0.04, 0.21 AE 0.04, 0.13 AE 0.03 and 0.09 AE 0.00 mg L À1 , respectively, obtained after 8 days of fermentation. The chemical structures of these antibiotics were determined by 1 H-and 13 C-nuclear magnetic resonance, mass and UV-visible data. The four new dithiolopyrrolone antibiotics -PR2, PR8, PR9 and PR10 -were characterized, respectively, as crotonyl-pyrrothine, sorbyl-pyrrothine, 2-hexonyl-pyrrothine and 2-methyl-3pentenyl-pyrrothine. The minimum inhibitory concentrations of the new induced antibiotics were determined.