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含硫氨基酸对阿尔及利亚糖丝菌NRRL B - 24137产生二硫代吡咯烷酮类抗生素的影响。

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

作者信息

Bouras N, Mathieu F, Sabaou N, Lebrihi A

机构信息

Ecole Nationale Supérieure Agronomique de Toulouse, INPT, Laboratoire de Génie chimique, Equipe Génie des Systèmes Microbiens, Castanet-Tolosan Cedex 1, Toulouse, France.

出版信息

J Appl Microbiol. 2006 Feb;100(2):390-7. doi: 10.1111/j.1365-2672.2005.02762.x.

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.

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.

摘要

目的

研究含硫氨基酸(L-半胱氨酸、L-胱氨酸、L-蛋氨酸和DL-乙硫氨酸)对阿尔及利亚糖丝菌NRRL B-24137产生二硫代吡咯烷酮类抗生素的影响。

方法与结果

在化学半合成培养基中,采用高效液相色谱法研究二硫代吡咯烷酮的产生水平。所研究抗生素的产生取决于这些来源在培养基中的性质、浓度和添加时间。半胱氨酸和胱氨酸均有利于二硫代吡咯烷酮的特异性产生;当最初添加到培养基中时,半胱氨酸有利于异丁酰-吡咯硫素(ISP)的产生,而胱氨酸有利于丁酰-吡咯硫素、千里光酰-吡咯硫素和惕各酰-吡咯硫素的产生。如图3所示,对于硫藤黄菌素,在存在5 mmol l(-1)胱氨酸时观察到二硫代吡咯烷酮的最大特异性产生;对于ISP,在存在5 mmol l(-1)半胱氨酸时;对于其他所研究的二硫代吡咯烷酮,在存在10 mmol l(-1)胱氨酸时。当半胱氨酸和胱氨酸浓度过高时,这些抗生素的产生会降低。添加蛋氨酸和乙硫氨酸会强烈抑制所有二硫代吡咯烷酮的特异性产生,但不抑制菌丝体生长。

结论

在所有研究的氨基酸中,胱氨酸和半胱氨酸可作为补充剂,用于提高阿尔及利亚糖丝菌NRRL B-24137产生二硫代吡咯烷酮类抗生素的产量。

研究的意义和影响

二硫代吡咯烷酮类抗生素作为药物有许多重要应用,特别是在治疗人类和动物癌症方面。在本研究中,研究了含硫氨基酸对二硫代吡咯烷酮类抗生素产生的影响。所得结果可用于优化培养基,以更高产量生产二硫代吡咯烷酮。

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