Integrated membrane-process boosting productivity and product yield of pharmaceutical protein production

produces lactic acid from sugars asintegral part of its primary energy metabolism,and if the cells are provided with sufficient glu-cose, growth as well as protein production willbe limited by accumulation of lactic acid in thefermentation broth. Inhibition of growth andprotein production can be delayed, but not pre-vented by titration of the lactic acid with base.Lactic acid and lactate also serve to induce pro-duction with the P170 system promoter; againthe inducing concentration will be higher if pHis kept high with base addition. At a given pHvalue, the optimal inducing level of lactate willbe severely but not absolutely growth inhibiting. The patented electro-membrane separationprocess, REED, provides a technology forremoving lactate from fermentation broth, whileretaining cells, proteins, sugars and most otherfeed components [2]. When the process is con-trolled to keep a constant pH in the fermenter,the amount of lactate in the broth will also bekept constant. This means that the level ofgrowth inhibition and of expression systeminduction can be controlle d during fermentation. The same principles used for the P170expression system in this abstract can be trans-ferred to other fermentation and expression sys-tems whether mammalian or bacterial.