A key challenge in metabolic engineering is to design novel or to improve existing biosynthetic pathways that lead to the cellular production of a given industrial or pharmaceutical compound. In many cases, the required enzymatic reactions for the biosynthesis of the target molecule need to be designed from scratch. BNICE.ch is a method that enables the design of de novo synthetic pathways through the postulation of novel biotransformations. However, finding enzymes that can potentially catalyze the proposed reactions remains a challenge. In this work, we propose a novel method, named BridgIT, to link novel reactions with well characterized enzymatic reactions and their associated genes. BridgIT compares every predicted novel reaction to all known enzymatic reactions for which a protein sequence is available. Novel and known reactions are compared based on the similarity of the reactive site of the substrates and the breakage and formation of atomic bonds during the conversion of the substrate to the product. As a result, BridgIT reports a similarity score for each comparison of known reactions to novel reactions, thus giving an estimate of the likelihood that a given enzyme can catalyze a novel reaction. The candidate proposed enzymes for de novo reactions by BridgIT, are either capable of catalyzing these reactions or they can serve as good initial sequences for the enzyme engineering. BridgIT online tool is freely available on the web (http://lcsb-databases.epfl.ch/) for academia upon subscription