An evolutionary approach was applied to create five generations of alpha -Al2O3-supported multi-metal-oxides to be used as catalytic materials for the oxidative dehydrogenation of propane at 773 K. Each generation consisted of 56 differently composed materials, i.e., a total amount of 280 materials. These catalytic materials were tested in parallel. For the best materials propene yields from 7% (Ist generation) to 9% (5th generation) were achieved. Some of these superior catalysts were characterised by XRD, XPS and EPR. A correlation between catalytic performance and the Mg/V ratio on the surface was found. Based on the structural knowledge obtained, from which the requirement of isolated or at least weakly interacting vanadium sites was derived, VOx (2.8 wt. %)/MCM-48 and VOx (2.8 wt. %)/MCM-41 catalysts with a high dispersion of vanadia were used as reference giving a maximal propene yield of 17 and 15%, respectively.