ABSTRACT Clavulanic acid is a β-lactam compound with potent inhibitory activity against β-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA production. Firstly, the influence of the primary nitrogen source and the salts composition was investigated. Subsequently, soybean protein isolate was supplemented with arginine (0.0–3.20 g L-1), threonine (0.0–1.44 g L-1), ornithine (0.0–4.08 g L-1), and glutamate (0.0–8.16 g L-1), according to a two-level central composite rotatable design. A medium containing ferrous sulfate yielded CA production of 437 mg L-1, while a formulation without this salt produced only 41 mg L-1 of CA. This substantial difference suggested that Fe2+ is important for CA biosynthesis. The experimental design showed that glutamate and ornithine negatively influenced CA production while arginine and threonine had no influence. The soybean protein isolate provided sufficient C5 precursor for CA biosynthesis, so that supplementation was unnecessary. Screening of medium components, together with experimental design tools, could be a valuable way of enhancing CA titers and reducing the process costs.

The second generation (2G) ethanol obtained from lignocellulosic biomass has been considered as a potential alternative source of energy for the transportation sector. However, the technologies to convert lignocellulose into fermentable sugars still face several challenges. One of the major challenges of this process is related to the cost of the cellulolytic enzymes. Thus, the development of bioprocesses for enzyme production and strategies to increase the final yield of the enzymatic hydrolysis reactions are required to ensure the economic feasibility of the biomass conversion process. In this review, it is discussed the progress related to fungal enzyme technology over the past few years with major emphasis on the biocatalysts needed for cellulose degradation as well as on cultivation strategies for the production of enzymes on-site. The potential of applying secretome analysis as a tool for the characterization of the enzymatic complexes and some limitations on the use of enzymatic cocktails in the saccharification step, such as the unproductive adsorption of enzymes onto lignin are also discussed in light of the recent literature.

The aim of this work was to compare the composition of a complex and soluble culture medium to eight other media described in the literature through the batch cultivation in a conventional bench-scale bioreactor for the production of cephamycin C by a wild strain of Streptomyces clavuligerus. The proposed medium resulted in an antibiotic production 1.5 to 7.5 times higher than the other culture media.

O ácido clavulânico (AC) é um importante inibidor de beta-lactamases, enzimas que degradampartir do metabolismo secundário do Streptomyces clavuligerus, bactéria filamentosa e estritamente aeróbia. Considerando que a velocidade de produção de metabólitos secundários está ligada à concentração celular, o presente trabalho teve como objetivo comparar a produção de AC nos processos contínuos com e sem reciclo celular e em batelada, realizando cultivos dessa bactéria com alta densidade celular. Para cumprir com o objetivo proposto, foram realizados experimentos em biorreator operando na forma contínua com reciclo utilizando-se um módulo de filtração tangencial de fibra oca para a separação celular. Os processos contínuos sem reciclo e em batelada foram realizados de forma convencional. A produtividade em AC no cultivo contínuo com reciclo celular (22,2 mg.L-1h-1) foi superior aos processos convencionais, apesar de obter-se maior concentração do produto (470 mg.L-1) em batelada.

The aim of the present work was to compare CA production in continuous culture with and without cell recycling and in batch process by Streptomyces clavuligerus. Continuous cultivations with high cell concentration using cell recycling were performed utilizing a hollow fiber ultrafiltration module to separate cells from the filtrate broth. The continuous cultures without cell recycling and the batch cultivations were performed conventionally. The highest productivity was attained in the continuous cultivation with cell recycling (22.2 mg.L-1.h-1). The highest CA concentration was obtained in the batch process (470 mg.L-1.h-1).