Phenolic acid esters have various potential uses as functional food ingredients, e.g., as antioxidants and preservative agents. Combinatorial mixtures of phenolic acid esters were generated by mixing several different alcohol and acid substrates in various combinations and esterifying enzymically. It was shown to be feasible to identify all the combinatorial products using LCMS and to separate the individual components by HPLC for separate bioassay. Ester mixtures were tested, in comparison with un-esterified substrate mixtures, for anti-microbial effects and found to be active against strains of human gut bacteria. Esterification did not increase the strength of the activity, but significant synergies, both positive and negative, between the components of different ester mixtures were found. Isolated components of a mixture had much less activity than the mixture itself. In tests for protection of cultured cells from H2O2-induced oxidative damage and consequent apoptosis, esterification could increase the strength of protection, possibly because of increased bioavailability of the more membrane-soluble hydrophobic esters, compared with the water-soluble substrates. The combinatorial enzymic approach to generation of synergistic mixtures of phenolic acid esters has potential to find synergistic combinations that would be missed by testing individual compounds and combining only the active compounds. (c) 2006 Elsevier Inc. All rights reserved.