the advantages of screening a small but high-quality enzyme library with verified activities. Especially in the case of enzymes with large, hydrophobic binding sites, precise predictions of enzyme-substrate interactions are difficult. Estimating the binding free energy with the MM-PBSA method correlated poorly with our experimental results. The library investigated here contains for each of the four substrates 2a-d at least one variant with the desired properties for the application in the cascade reaction shown in Scheme 1. These are the suppression of O-methylation of the phenolic acids 1 and higher activity towards the intermediate phenolic styrenes 2.