title: Identification of Enzyme Genes Using Chemical Structure Alignments of Substrate-Product Pairs.
abstract: Although there are several databases that contain data on many metabolites and reactions in biochemical pathways, there is still a big gap in the numbers between experimentally identified enzymes and metabolites. It is supposed that many catalytic enzyme genes are still unknown. Although there are previous studies that estimate the number of candidate enzyme genes, these studies required some additional information aside from the structures of metabolites such as gene expression and order in the genome. In this study, we developed a novel method to identify a candidate enzyme gene of a reaction using the chemical structures of the substrate-product pair (reactant pair). The proposed method is based on a search for similar reactant pairs in a reference database and offers ortholog groups that possibly mediate the given reaction. We applied the proposed method to two experimentally validated reactions. As a result, we confirmed that the histidine transaminase was correctly identified. Although our method could not directly identify the asparagine oxo-acid transaminase, we successfully found the paralog gene most similar to the correct enzyme gene. We also applied our method to infer candidate enzyme genes in the mesaconate pathway. The advantage of our method lies in the prediction of possible genes for orphan enzyme reactions where any associated gene sequences are not determined yet. We believe that this approach will facilitate experimental identification of genes for orphan enzymes.
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Moriya
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology , 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Graduate School of Medical and Dental Sciences, Niigata University , 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.
authors.forename: Shujiro
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Zenichi
authors.initials: Z
authors.lastname: Nakagawa
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology , 2-12-1 Ookayama, Meguro-ku, Tokyo, 152-8550, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kotera
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tokimatsu
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanehisa
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Goto
mesh_terms: D030562:Databases, Protein; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004798:Enzymes