Improved fed-batch bioprocesses using chemically modified amino acids in concentrated feeds

Background Fed-batch culture bioprocesses are essential for the production of therapeutic proteins [1]. In these cultures, concentrated feeds are added during cultivation to prevent nutrient depletion and to extend the growth phase, thus increasing product concentration [2]. One limitation arises from the low solubility of some amino acids at high concentrations, in particular tyrosine [3]. This amino acid is commonly solubilized in separate feeds at basic pH [4] inducing pH spikes and precipitation when added in the bioreactor. This work describes the evaluation of several chemically modified tyrosines as alternative to simplify fed-batch bioprocesses by using single feeding strategies at neutral pH.