Effects of methanol on expression of an anticoagulant hirudin in recombinant Hansenula polymorpha

A series of batch, fed-batch, and continuous cultures was carried out to an alyze the effects of methanol on the fermentation characteristics of recomb inant Hansenula polymorpha for the production of hirudin, an anticoagulant. Hirudin expression efficiencies were greatly influenced by the methanol co ncentrations in continuous and fed-batch culture modes. At a steady state o f continuous culture, an optimum methanol concentration of 1.7 g l(-1) was determined ata dilution rate of 0.18 h(-1) with 1.8 mg l(-1) h(-1) hirudin productivity.