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

Author(s)

Leite, Carla A. ^[1] ; Cavallieri, Andre P. ^[1] ; Araujo, Maria L. G. C. ^[1]

Affiliation

^[1] UNESP, Sao Paulo State Univ, Dept Biochem & Technol Chem, BR-14800900 Araraquara, SP - Brazil

• Document type: Journal article
• Source: BMC Microbiology; v. 13, DEC 20 2013.
• Web of Science Citations: 2

Abstract

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. (AU)

• FAPESP's process: 13/02632-4 - Metabolic flux analysis for the in silico optimization of the production of biocompounds by Streptomyces clavuligerus
• Grantee: Maria Lucia Gonsales da Costa Araujo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 05/55079-4 - Production and purification of clavulanic acid, cephamycin C and other bioactive metabolites of Streptomyces
• Grantee: Carlos Osamu Hokka
• Support Opportunities: Research Projects - Thematic Grants