Overflow metabolism characterizes cells strains that are likely to produce inhibiting metabolites resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. This paper proposes two non-model based extremum-seeking strategies preventing a too important accumulation of inhibiting metabolites in fed-batch cultures, by estimating the critical substrate level on the basis of 3 simple measurements related to the feeding, oxygen and carbon dioxide. A simple substrate controller based on Lyapunov stability arguments is then designed and tested in combination with the two extremum-seeking schemes.