Fed-batch cultures of Escherichia coli are commonly used for the production of biopharmaceuticals. However, productivity can be adversely affected by the production of acetate inhibiting the cell respiratory capacity. In this study, a nonlinear predictive control is developed based on a process model, and an unscented Kalman filter for estimating the evolution of the glucose and acetate concentrations. The control objective is to regulate the acetate concentration at a low level, so as to maintain the culture close to the edge between the fermentative and respirative regimes. The control strategy is tested in simulation and in lab-scale experiments, demonstrating its feasibility and performance.