Decarboxylation of caffeic acid, p-coumaric acid, ferulic acid, and sinapic acid for the synthesis of 2a-d was achieved according to the literature. All reactions were performed on a 1 mL scale in 1.5 mL reaction tubes. The respective substrate pre-dissolved in DMSO (200 mM stock) was mixed with the reaction buffer (50 mM potassium phosphate buffer, pH 6), to reach a final concentration of 10 mM. The reaction was initiated after the addition of the respective amount of the lyophilized enzyme (typically 0.4 mg mL -1 ) or the CFE of variant I85A (100 mg mL -1 ) in the case of 2d while incubated at 30 °C with 600 rpm in a Thermomixer. When the full conversion was detected by TLC (cyclohexane/ ethyl acetate= 1/1, CAM or UV), samples of 150 μL were taken and extracted with MTBE (2×100μL). The combined organic layers were dried over Na2SO4 and after mixing and centrifugation to allow precipitation of Na2SO4, the supernatant could be used for GC-MS analysis. For HPLC analysis, samples of 100 μL were taken and quenched by the addition of 150 μL ACN (containing 400 mM HCl). After centrifugation to allow enzyme precipitation, the supernatant was used for HPLC measurements. All substrates were fully converted after 1 h. The aforementioned reaction solution was used as stock for the methylation reaction. The appropriate volume of that solution was added to a new vial containing the buffer for the methylation (100 mM Tris-HCl, pH 7.5, 5 mM MgCl2, 0.5 mM DTT) to reach a final substrate concentration of 1 mM followed by the addition of 5 μΜ of the purified enzyme and 2 mM SAM. Reactions were incubated at 25 °C with 750 rpm in a Thermomixer. The final reaction volume was 150 μL. Samples were taken after 0 and 24 h and an equal volume of acetonitrile (100 mM HCl) was added to quench the reaction. The samples were centrifuged at full speed for 60 min and then 200 μL supernatant was transferred to microwells before HPLC analysis. The wavelength chosen for the detection of the methylated products is 305 nm.