Effect of amino acids containing sulfur on dithiolopyrrolone antibiotic productions by Saccharothrix algeriensis NRRL B-24137

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Abstract
Aims: 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 semi‐synthetic 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 butanoyl‐pyrrothine, 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 Fig. 3. 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. Effect of cysteine () and cystine () addition at different concentrations on specific production of thiolutin (a), senecioyl‐pyrrothine (b), tigloyl‐pyrrothine (c), iso‐butyryl‐pyrrothine (d) and butanoyl‐pyrrothine (e). Specific dithiolopyrrolone productions are given as mg per g of biomass at the time of maximal productions during 96 h of fermentation. 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.

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