초록
<P><B>Highlights</B></P><P>► The paper contributes to fill the gap existing between the basic and applied research. ► Mathematical model sheds light on the physiology of auxotrophic yeast strains. ► Yeast behavior in fed-batch is influenced by biological and environmental determinants. ► Process optimization would make possible the production of heterologous proteins which are not yet on the market.</P> <P><B>Abstract</B></P><P>A systematic investigation on the effects of auxotrophies on the performance of yeast in aerated fed-batch reactor was carried out. Six isogenic strains from the CEN.PK family of <I>Saccharomyces cerevisiae</I>, one prototroph and five auxotrophs, were grown in aerated fed-batch reactor using the same operative conditions and a proper nutritional supplementation. The performance of the strains, in terms of final biomass decreased with increasing the number of auxotrophies. Auxotrophy for leucine exerted a profound negative effect on the performance of the strains. Accumulation of reactive oxygen species (ROS) in the cells of the strain carrying four auxotrophies and its significant viability loss, were indicative of an oxidative stress response induced by exposure of cells to the environmental conditions. The mathematical model was fundamental to highlight how the carbon flux, depending on the number and type of auxotrophies, was diverted towards the production of increasingly large quantities of energy for maintenance.</P>