Fed-batch cultivation involves a controlled, continuous or intermittent feed of substrate into a closed bioreactor without continuous removal of culture. It avoids: (1) substrate inhibition (too much substrate is toxic), (2) catabolite repression (e.g. glucose repression of secondary metabolite formation), and (3) overflow metabolism (e.g. acetate formation in E. coli). It is the dominant mode in industrial production of antibiotics, amino acids, and recombinant proteins.