Multicomponent mixtures incurred in enzyme-catalyzed reactions are often difficult to separate. In this paper a systematic approach is presented for developing the scheme of a complex process using supercritical fluid extraction (SFE) in order to separate such mixtures. As a model system representative of many enzymatic reactions, the transesterification of ethyl acetate (EAC) and isoamyl alcohol (IAL) yielding ethanol (EAL) and isoamyl acetate (IAC) in supercritical CO2 is chosen. The separation strategy is based on first separating two fractions of components with significantly different solubilities in CO2. Subsequently, the separation of the substances in each fraction is effected. Parts of the SFE process are simulated by modelling countercurrent extraction columns. In modelling, the Soave-Redlich-Kwong equation of state (SRK equation) is used for describing the phase equilibria of the model system. An efficient scheme is proposed combining the reaction and the separation in an integrated process using CO2 as the unique solvent.