The motivation behind this proposal is best summarised in the words of Thomas Alva Edison: Until man reproduces a blade of grass Nature will laugh at our so-called scientific knowledge. This proposal is part of a long-term effort aimed at reproducing Nature s remarkable ability to generate molecular machines that perform at levels near perfection. Most biological processes involve the action of enzymes, which are central for explaining the workings of living cells and organisms. However, there is no comprehensive quantitative understanding of enzyme action and our current understanding certainly fails the most severe test ? that of producing catalysts with rates that rival natural enzymes. We want to address this complex question by evolution experiments in the test tube, harnessing the forces of Darwinian evolution. The evolutionary snapshots should then tell us how a catalytic machineries involved in signalling cascades and the biosyntheis of un-natural natural products (as potential drug candidates) are built up ? and generate useful reagents that may make it possible to probe signaling pathways and make new potential drug candidates.