A spatiotemporal metabolic model of a representative syngas bubble-column reactor was applied to design and evaluate dynamic matrix control (DMC) schemes for regulation of the desired by-product ethanol and the undesired by-product acetate. This model was used to develop linear step response models for controller design and also served as the process in closed-loop simulations. A 2x2 DMC scheme with manipulation of the liquid and gas feed flows to the column provided a superior performance to proportional integral (PI) control due to slow process dynamics combining the multivariable and constrained nature of the control problem. Ethanol concentration control for large disturbances was further improved by adding the flow of a pure hydrogen stream as a third manipulated variable. The advantages of DMC for syngas bubble-column reactor control are demonstrated and a design strategy for future industrial applications is provided.