EXPRESSION OF HIRUDIN IN FED-BATCH CULTURES OF RECOMBINANT SACCHAROMYCES-CEREVISIAE

Fed-batch fermentations were performed to produce hirudin, an anticoag ulant protein, from recombinant S. cerevisiae. The structural gene cod ing for hirudin was combined with the GAL10 promoter for controlled ex pression and the MF alpha 1 signal sequence for secretion to the growt h medium. Control of galactose concentration in a fed-batch mode of op eration 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 i ncrease in cell density and a 4.1-fold enhancement In hirudin concentr ation compared with the batch fermentation.