Avaliação do processo de produção de cefamicina C por Streptomyces clavuligerus

Abstract

Streptomyces clavuligerus produces various beta-lactam compounds, especially the cephamycin C. Some authors suggest that the nature and concentration of carbon and nitrogen added to the culture medium may favor the production of larger quantities of the antibiotic. Lysine plays an important role in Streptomyces clavuligerus, acting on its catabolism, via cadaverine, and secondary metabolism, in which it is converted via 1-piperideine-6-carboxylate to alpha-aminoadipic acid, a beta-lactam antibiotic precursor. The role of lysine as a cephamycin C inducer, when added to production medium at concentrations above 50 mM, has been widely explored in the literature. Moreover there are some reports on the positive influence of multifunctional diamines and antibiotic precursor compounds such as alpha-ketoglutarate. However, there is not studies on the combined influence of these inducers on beta-lactam antibiotic production. Thus, this Thesis explores such influences to devise a culture medium economically viable and which promotes the production of cafamicina C. For this, we evaluated the effect of culture medium (synthetic, semi-synthetic or complex), carbon source (starch or maltose) and different modes of operation (batch or continuous culture). Was adopted the Response Surface Methodology to investigate the interaction of lysine with putrescine or 1,3-diaminopropane and its influence on cephamycin C biosynthesis of Streptomyces clavuligerus. The addition of lysine (100 mM) in basal medium (without additives) led to an cephamycin C production of 120 mg/L, an increase of 445% in the production of this antibiotic. However, there was a residual of 30 mM at the end of cultivation, becoming the process uneconomical. The addition of putrescine (0.2 g/L) and lysine (40 mM) in the culture medium with maltose as a carbon source, showed a production around 150 mg/L in the intermittent cultivation mode. However, in this mode of operation, the increased ...