Methionine is one of the essential amino acids produced by fed-batch fermentation. The synthesis of methionine at the cellular level is strictly regulated and its process dynamics shows a nonlinear interaction between dissolved oxygen and glucose concentration. For controlling this process, a decoupled input-output linearizing controller (DIOLC) is derived. The model used for this purpose contains an exponential kinetic structure for describing the nonlinearities and metabolic switching function for describing oxygen dependency. The control system is square having two inputs and two outputs. The zero dynamics stability for internal variables and error convergence is proved. The performance of DIOLC is examined under high and low oxygen demand conditions. Four case studies are used to demonstrate that the DIOLC action is decoupled. The DIOLC also exhibited robust performance even for random variations up to +/- 20% in some parameters. In simulated experiments, using DIOLC produces 16 g l(-1) of methionine. The performance of PI controllers under identical conditions is given for comparison. (C) 2008 Published by Elsevier Ltd.