Enhancing effect of lysine combined with other compounds on cephamycin C production in Streptomyces clavuligerus

BMC Microbiology

Maria L G C Araujo¹  André P Cavallieri¹  Carla A Leite¹ 

[1] Department of Biochemistry and Technological Chemistry, UNESP - São Paulo State University, Institute of Chemistry, 14800-900 Araraquara, SP, Brazil

关键词: Response surface;    Alpha-aminoadipic acid;    Diamines;    Lysine;    Cephamycin C;    Streptomyces clavuligerus;   

Others  :  1142288
DOI  :  10.1186/1471-2180-13-296

 received in 2013-08-12, accepted in 2013-12-18,  发布年份 2013

【 摘 要 】

Background

Lysine plays an important role in Streptomyces clavuligerus metabolism; it takes part in its catabolism, via cadaverine, and in its secondary metabolism, in which lysine is converted via 1-piperideine-6-carboxylate to alpha-aminoadipic acid, a beta-lactam antibiotic precursor. The role of lysine as an enhancer of cephamycin C production, when added to production medium at concentrations above 50 mmol l^-1, has already been reported in the literature, with some studies attributing a positive influence to multifunctional diamines, among other compounds. However, there is a lack of research on the combined effect of these compounds on antibiotic production.

Results

Results from experimental design-based tests were used to conduct response surface-based optimization studies in order to investigate the synergistic effect of combining lysine with cadaverine, putrescine, 1,3-diaminopropane, or alpha-aminoadipic acid on cephamycin C volumetric production. Lysine combined with cadaverine influenced production positively, but only at low lysine concentrations. On the whole, higher putrescine concentrations (0.4 g l^-1) affected negatively cephamycin C volumetric production. In comparison to culture media containing only lysine as additive, combinations of this amino acid with alpha-aminoadipic acid or 1,3-diaminopropane increased cephamycin C production by more than 100%.

Conclusion

This study demonstrated that different combinations of lysine with diamines or lysine with alpha-aminoadipic acid engender significant differences with respect to antibiotic volumetric production, with emphasis on the benefits observed for lysine combined with alpha-aminoadipic acid or 1,3-diaminopropane. This increase is explained by mathematical models and demonstrated by means of bioreactor cultivations. Moreover, it is consistent with the positive influence of these compounds on lysine conversion to alpha-aminoadipic acid, a limiting step in cephamycin C production.

【 授权许可】

   
2013 Leite et al.; licensee BioMed Central Ltd.

【 图 表 】

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