Expression of hirudin in fed-batch cultures of recombinant Saccharomyces cerevisiae

Fed-batch fermentations were performed to produce hirudin, an anticoagulant protein, from recombinant S. cerevisiae. The structural gene coding for hirudin was combined with the GAL10 promoter for controlled expression and the MFα1 signal sequence for secretion to the growth medium. Control of galactose concentration in a fed-batch mode of operation yielded 110 g/L of final cell density and 260 mg/L of maximum hirudin concentration in the medium, which corresponds to a 3.5-fold increase in cell density and a 4.1-fold enhancement in hirudin concentration compared with the batch fermentation.ope