title: Enhancing effect of lysine combined with other compounds on cephamycin C production in Streptomyces clavuligerus.
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%.
  
  
  CONCLUSIONS
  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.
authors.forename: Carla A
authors.initials: CA
authors.lastname: Leite
authors.forename: André P
authors.initials: AP
authors.lastname: Cavallieri
authors.affiliation: Department of Biochemistry and Technological Chemistry, UNESP - São Paulo State University, Institute of Chemistry, 14800-900 Araraquara, SP, Brazil. mlaraujo@iq.unesp.br.
authors.forename: Maria L G C
authors.initials: ML
authors.lastname: Araujo
mesh_terms: D015074:2-Aminoadipic Acid / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002513:Cephamycins / Q000096:biosynthesis*; D003470:Culture Media / Q000737:chemistry; D003959:Diamines / Q000378:metabolism; D006801:Humans; D007218:Industrial Microbiology / Q000379:methods; D008239:Lysine / Q000378:metabolism*; D008962:Models, Theoretical; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002513:Cephamycins; D003470:Culture Media; D003959:Diamines; D015074:2-Aminoadipic Acid; D008239:Lysine; C024925:cephamycin C