Clavulanic acid production by the MMS 150 mutant obtained from wild type Streptomyces clavuligerus ATCC 27064

Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064). The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant.

Comparisons between continuous and batch processing to produce clavulanic acid by Streptomyces clavuligerus

O ácido clavulânico (AC) é um importante inibidor de b-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.

Effect of the carbon sources on the growth kinetics of Cephalosporium acremonium in the Cephalosporin C production process

The growth phase of Cephalosporium acremonium ATCC 48272 was analized in the batch production process of cephalosporin C. Two media were used: one containing glucose and sucrose as main sources of carbon and energy, and the other containing only glucose. The consumption rate of glucose to form biomass was much higher in medium containing only glucose. The behavior in both media could be satisfactorily explained though simulation of a model which included inibition of glucose comsumption by sucrose in the classical Contois kinetics.