Optimization of cultural conditions for enhancing the expression of human interferon-α2a by recombinant yeast

Abstract

When adenine (Ade) was added to basal culture medium at 12 h after inoculation, antivirus activity and specific activity of interferon-α2a (IFN-α2a) were increased. Expression of IFN-α2a was realized when a low residual glucose concentration was maintained during the mid- and late-phase of cultivation. In addition, biological activity and specific activity of IFN-α2a were increased by more than 100% if the ratio of glucose and sucrose in the basal medium was 1:0.1. The addition of glutamate also led to the intensive enhancement of the expression level of IFN-α2a. The initial pH of the basal medium proved to be crucial to the expression level. When the above optimal cultivation condition obtained in the shake flask was applied to the fed-batch culture using a 2.6 l jar fermenter, human IFN-α2a biological activity reached 1.3×10 7 IU/ml, which was four times that of the control.