Optimal strategy of pH control in the production of recombinant human epidermal growth factor by Hansenula polymorpha

Abstract

The pH dependency of cell growth and human epidermal growth factor (hEGF) production was studied with a recombinant Hansenula polymorpha strain. Maximum specific growth rate and apparent specific production rate of hEGF was highly dependent on culture pH over the range of 4.0–7.0. The optimal pH for the fastest growth was 5.0 and for the apparent production of hEGF 6.0. A simple kinetic model considering the degradation of hEGF during culture was established. Then it was used to estimate the intrinsic specific production rate of hEGF and simulate expression behavior according to culture pH. The intrinsic specific production rate of hEGF was relatively unaffected by culture pH over the range of 5.0–7.0. An optimal pH switching time exists for a given methanol concentration in the fed-batch culture maintaining constant methanol concentration.