Combined available nitrogen resources enhanced erythromycin production and preliminary exploration of metabolic flux analysis under nitrogen perturbations.

Abstract

In the current study, the effect of different available nitrogen sources on erythromycin fermentation by Saccharopolyspora erythraea No. 8 is evaluated. Three different combinations of corn steep liquor and yeast powder were developed to investigate their impacts on erythromycin production. The results indicate that the optimal combination of available nitrogen sources was 10.0g/L corn steep liquor and 4.0g/L yeast power, generating a maximum yield of erythromycin of 13672 U/mL. To explore the effects of nitrogen perturbations on cell metabolism, metabolic flux analyses were performed and compared under different conditions. A high flux pentose phosphate pathway provided more NADPH for erythromycin synthesis via nitrogen optimization. Moreover, high n-propanol specific consumption rate enhanced erythromycin synthesis and n-propanol flowed into the central carbon metabolism by methylmalonyl-CoA node. These results indicate that the selection of an appropriate organic nitrogen source is essential for cell metabolism and erythromycin synthesis, and this is the first report of the successful application of available nitrogen source combinations in industrial erythromycin production.