Nutritional requirements for the production of dithiolopyrrolone antibiotics by Saccharothrix algeriensis NRRL B-24137 |
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| Affiliation: | 1. Département Bioprocédés et Systèmes Microbiens, Laboratoire de Génie Chimique, UMR 5503 (CNRS/INPT/UPS), École Nationale Supérieure Agronomique de Toulouse, Institut National Polytechnique de Toulouse, 1, avenue de l’Agrobiopôle, B.P. 32 607, F-31 326 Castanet-Tolosan Cedex 1, France;2. Laboratoire de Recherche sur les Produits Bioactifs et la Valorisation de la Biomasse, École Normale Supérieure d’Alger, B.P. 92, 16 050 Vieux-Kouba, Alger, Algeria;1. Bristol-Myers Squibb Drug Discovery, Wallingford, CT 06492, USA;2. Bristol-Myers Squibb, Drug Product Science & Technology, Princeton, NJ 08543, USA;1. Children’s Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA;2. Department of Physiology and Developmental Biology, College of Life Sciences, Brigham Young University, Provo, UT 84602, USA;3. Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, Sioux Falls, SD 57104, USA;1. Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;2. Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan;3. RIKEN Center for Life Science Technologies, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan |
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| Abstract: | The amino acid and humic acid requirements of Saccharothrix algeriensis NRRL B-24137 for growth and production of the dithiolopyrrolone antibiotics were studied in a semi-synthetic medium (SSM). Nature and concentration of amino acids and humic acid strongly influenced the growth and dithiolopyrrolone specific production.The highest value of thiolutin (acetyl-pyrrothine) specific production was obtained in the presence of 1 g/l humic acid (336 mg/g DCW), and in the presence of 5 mM l-cystine (309 mg/g DCW) as compared to 19 mg/g DCW obtained with the control. Furthermore, thiolutin production was increased about six-fold, four-fold and three-fold in the presence of l-proline, l-glutamic acid and dl-histidine, respectively. In contrast, the production of thiolutin was reduced by addition of other amino acids such as l-glutamine, dl-ethionine, l-methionine and l-arginine. The highest value of isobutyryl-pyrrothine production was obtained in the presence of 2,6-diaminopimelic acid and l-lysine (7.8 and 1.0 mg/g DCW, respectively). However, the highest value of butanoyl-pyrrothine production was obtained in the presence of humic acid (6.6 mg/g DCW), followed by l-cysteine and l-proline (3.6 and 3.2 mg/g DCW, respectively). In addition, the maximum specific production of senecioyl-pyrrothine (29 mg/g DCW) and tigloyl-pyrrothine (21 mg/g DCW) was obtained in the presence of humic acid. We found that, except for isobutyryl-pyrrothine, production of all dithiolopyrrolones was favoured by addition of l-proline. The maximum specific production was obtained with l-proline at concentrations of 2.50 mM for thiolutin (133 mg/g DCW), 1.25 mM for senecioyl-pyrrothine, tigloyl-pyrrothine and butanoyl-pyrrothine production (29, 23 and 3.9 mg/g DCW, respectively). Production of all dithiolopyrrolones strongly decreased as the l-methionine or dl-ethionine concentration was increased in the culture medium. |
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