We used RDKit () to visualize attention weights on the molecular structure of substrates. We used ProDy () and PyMol () to visualize attention weights and MD-identified important residues on the structure of enzymes. The 90 th percentile of the probability distribution of attention weights was considered the threshold to identify important residues. According to the Continuous Bag-of-Words mechanism, the number of attention weights extracted is two less than the number of amino acids; therefore, we set the attention weight of an amino acid as the highest attention weight in three neighboring amino acids and then selected the important amino acids according to the threshold. Gene site mutagenesis. The residue sites for mutation were selected according to attention weights, including four proximal sites (distance to substrate <10 Å) and four distal sites (distance to substrate >10 Å). Gene site mutagenesis was achieved using a ClonExpress Ultra One Step Cloning Kit (Vazyme Biotech, Nanjing) as per the manufacturer's protocol. The pD2P plasmids with genes ZH4 and OH1 were used as PCR templates to generate point mutations in selected residues of ZH4 and OH1. The sequence of each variant was confirmed through sequencing. Finally, the pD2P plasmids with point mutation on genes ZH4 (index of amino acid residues: 12, 21, 32, and 134) and OH1 (index of amino acid residues: 101, 169, 255, and 348) were expressed and assayed for their mycotoxin degradation activity, as described in the sections on the evaluation of the catalytic activity of candidate enzymes. The experiments were independently performed three times (n=3 biologically independent samples), and at least two technical replicates were used in each experimental group. and ZEA in the Rhea database. (F, G) The most similar reactions with OTA and ZEA hydrolysis reactions in the Rhea database. Molecular similarity was calculated using the maximum common substructure algorithm 2 . Reaction similarity was calculated based on the reaction difference fingerprint 3 and the Tanimoto algorithm 4 . Both hydrolysis reactions of ZEA and OTA are not included in the International Union of Biochemistry and Molecular Biology Enzyme Commission (EC) system 5 , indicating EC-based prediction methods (e.g., CLEAN 6 ) do not apply to these cases. were generated based on the weighted random sampling strategy. For enzymes/substrates with high specificity, more corresponding unlabeled (considered as negative) enzyme-substrate pairs were included in the dataset. For enzymes/substrates with high promiscuity, fewer corresponding unlabeled enzyme-substrate pairs were included in the dataset. (E, F) Ratios of unlabeled and positive enzyme-substrate pairs. The weighted random sampling strategy assumes that enzymes with fewer reported substrates have a higher catalytic specificity and enzymes with many reported substrates have a higher catalytic promiscuity.