Department of Biochemistry and Technological Chemistry, UNESP - São Paulo State University, Institute of Chemistry, 14800-900 Araraquara, SP, Brazil.
BMC Microbiol. 2013 Dec 20;13:296. doi: 10.1186/1471-2180-13-296.
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 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%.
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.
赖氨酸在棒状链霉菌代谢中起着重要作用；它参与了赖氨酸的分解代谢，通过尸胺，以及参与了次级代谢，其中赖氨酸通过 1-哌啶-6-羧酸转化为α-氨基己二酸，这是一种β-内酰胺抗生素前体。文献中已经报道了赖氨酸作为头孢菌素 C 生产的增强剂的作用，当在生产培养基中添加浓度高于 50mmol/L 时，一些研究将这种积极影响归因于多功能二胺等化合物。然而，目前缺乏关于这些化合物联合作用对抗生素生产影响的研究。
基于实验设计的测试结果用于进行基于响应面的优化研究，以研究赖氨酸与尸胺、腐胺、1,3-二氨基丙烷或α-氨基己二酸联合使用对头孢菌素 C 体积生产的协同作用。赖氨酸与尸胺联合使用对生产有积极影响，但仅在低赖氨酸浓度下。总的来说，较高的腐胺浓度（0.4g/L）对头孢菌素 C 体积生产有负面影响。与仅含有赖氨酸作为添加剂的培养基相比，这种氨基酸与α-氨基己二酸或 1,3-二氨基丙烷的组合使头孢菌素 C 产量增加了 100%以上。
本研究表明，赖氨酸与二胺或赖氨酸与α-氨基己二酸的不同组合在抗生素体积生产方面存在显著差异，重点强调了赖氨酸与α-氨基己二酸或 1,3-二氨基丙烷组合的益处。这种增加可以通过数学模型来解释，并通过生物反应器培养来证明。此外，这与这些化合物对赖氨酸转化为α-氨基己二酸的积极影响是一致的，α-氨基己二酸是头孢菌素 C 生产的一个限制步骤。
