RESUMO
The physiology of feeding ammonium sulphate in erythromycin biosynthesis phase of Saccharopolyspora erythraea on the regulation of erythromycin A (Er-A) biosynthesis was investigated in 50 L fermenter. At an optimal feeding ammonium sulphate rate of 0.03 g/L per h, the maximal Er-A production was 8281 U/mL at 174 h of growth, which was increased by 26.3% in comparison with the control (6557 U/mL at 173 h). Changes in cell metabolic response of actinomycete were observed, i.e. there was a drastic increase in the level of carbon dioxide evolution rate and oxygen consumption. Assays of the key enzyme activities and organic acids of S. erythraea and amino acids in culture broth revealed that cell metabolism was enhanced by ammonium assimilation, which might depend on the glutamate transamination pathway. The enhancement of cell metabolism induced an increase of the pool of TCA cycle and the metabolic flux of erythromycin biosynthesis. In general, ammonium assimilation in the erythromycin biosynthesis phase of S. erythraea exerted a significant impact on the carbon metabolism and formation of precursors of the process for dramatic regulation of secondary metabolites biosynthesis.
Assuntos
Sulfato de Amônio/metabolismo , Eritromicina/biossíntese , Saccharopolyspora/metabolismo , Aminação/efeitos dos fármacos , Aminoácidos/metabolismo , Sulfato de Amônio/farmacologia , Reatores Biológicos , Dióxido de Carbono/metabolismo , Ciclo do Ácido Cítrico/efeitos dos fármacos , Fermentação/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Oxigênio/metabolismo , Saccharopolyspora/efeitos dos fármacosRESUMO
The model equations of the growth phase of rHSA fermentation were derived on the base of both elemental balance and metabolic balance. The unknown parameters of the model were estimated by multivariable optimization. The model can preferably describe the relations between different macroscopic reaction rates of the process and provide the key for the high-density cultivation of Pichia pastoris.