Prediction of missing enzyme genes in a bacterial metabolic network: Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa

Yoshihiro Yamanishi, Hisaaki Mihara, Motoharu Osaki, Hisashi Muramatsu, Nobuyoshi Esaki, Tetsuya Sato, Yoshiyuki Hizukuri, Susumu Goto, Minoru Kanehisa

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    The metabolic network is an important biological network which consists of enzymes and chemical compounds. However, a large number of metabolic pathways remains unknown, and most organism-specific metabolic pathways contain many missing enzymes. We present a novel method to identify the genes coding for missing enzymes using available genomic and chemical information from bacterial genomes. The proposed method consists of two steps: (a) estimation of the functional association between the genes with respect to chromosomal proximity and evolutionary association, using supervised network inference; and (b) selection of gene candidates for missing enzymes based on the original candidate score and the chemical reaction information encoded in the EC number. We applied the proposed methods to infer the metabolic network for the bacteria Pseudomonas aeruginosa from two genomic datasets: gene position and phylogenetic profiles. Next, we predicted several missing enzyme genes to reconstruct the lysine-degradation pathway in P. aeruginosa using EC number information. As a result, we identified PA0266 as a putative 5-aminovalerate aminotransferase (EC 2.6.1.48) and PA0265 as a putative glutarate semialdehyde dehydrogenase (EC 1.2.1.20). To verify our prediction, we conducted biochemical assays and examined the activity of the products of the predicted genes, PA0265 and PA0266, in a coupled reaction. We observed that the predicted gene products catalyzed the expected reactions; no activity was seen when both gene products were omitted from the reaction.

    Original languageEnglish
    Pages (from-to)2262-2273
    Number of pages12
    JournalFEBS Journal
    Volume274
    Issue number9
    DOIs
    Publication statusPublished - May 1 2007

    Fingerprint

    Metabolic Networks and Pathways
    Pseudomonas aeruginosa
    Lysine
    Genes
    5-aminovalerate aminotransferase
    glutarate-semialdehyde dehydrogenase
    Degradation
    Enzymes
    Bacterial Genomes
    Gene Order
    Association reactions
    Chemical compounds
    Bacteria
    Chemical reactions
    Assays

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Prediction of missing enzyme genes in a bacterial metabolic network : Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa. / Yamanishi, Yoshihiro; Mihara, Hisaaki; Osaki, Motoharu; Muramatsu, Hisashi; Esaki, Nobuyoshi; Sato, Tetsuya; Hizukuri, Yoshiyuki; Goto, Susumu; Kanehisa, Minoru.

    In: FEBS Journal, Vol. 274, No. 9, 01.05.2007, p. 2262-2273.

    Research output: Contribution to journalArticle

    Yamanishi, Y, Mihara, H, Osaki, M, Muramatsu, H, Esaki, N, Sato, T, Hizukuri, Y, Goto, S & Kanehisa, M 2007, 'Prediction of missing enzyme genes in a bacterial metabolic network: Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa', FEBS Journal, vol. 274, no. 9, pp. 2262-2273. https://doi.org/10.1111/j.1742-4658.2007.05763.x
    Yamanishi, Yoshihiro ; Mihara, Hisaaki ; Osaki, Motoharu ; Muramatsu, Hisashi ; Esaki, Nobuyoshi ; Sato, Tetsuya ; Hizukuri, Yoshiyuki ; Goto, Susumu ; Kanehisa, Minoru. / Prediction of missing enzyme genes in a bacterial metabolic network : Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa. In: FEBS Journal. 2007 ; Vol. 274, No. 9. pp. 2262-2273.
    @article{aa786430c4ee491298c8af0cdb5d3725,
    title = "Prediction of missing enzyme genes in a bacterial metabolic network: Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa",
    abstract = "The metabolic network is an important biological network which consists of enzymes and chemical compounds. However, a large number of metabolic pathways remains unknown, and most organism-specific metabolic pathways contain many missing enzymes. We present a novel method to identify the genes coding for missing enzymes using available genomic and chemical information from bacterial genomes. The proposed method consists of two steps: (a) estimation of the functional association between the genes with respect to chromosomal proximity and evolutionary association, using supervised network inference; and (b) selection of gene candidates for missing enzymes based on the original candidate score and the chemical reaction information encoded in the EC number. We applied the proposed methods to infer the metabolic network for the bacteria Pseudomonas aeruginosa from two genomic datasets: gene position and phylogenetic profiles. Next, we predicted several missing enzyme genes to reconstruct the lysine-degradation pathway in P. aeruginosa using EC number information. As a result, we identified PA0266 as a putative 5-aminovalerate aminotransferase (EC 2.6.1.48) and PA0265 as a putative glutarate semialdehyde dehydrogenase (EC 1.2.1.20). To verify our prediction, we conducted biochemical assays and examined the activity of the products of the predicted genes, PA0265 and PA0266, in a coupled reaction. We observed that the predicted gene products catalyzed the expected reactions; no activity was seen when both gene products were omitted from the reaction.",
    author = "Yoshihiro Yamanishi and Hisaaki Mihara and Motoharu Osaki and Hisashi Muramatsu and Nobuyoshi Esaki and Tetsuya Sato and Yoshiyuki Hizukuri and Susumu Goto and Minoru Kanehisa",
    year = "2007",
    month = "5",
    day = "1",
    doi = "10.1111/j.1742-4658.2007.05763.x",
    language = "English",
    volume = "274",
    pages = "2262--2273",
    journal = "FEBS Journal",
    issn = "1742-464X",
    publisher = "Wiley-Blackwell",
    number = "9",

    }

    TY - JOUR

    T1 - Prediction of missing enzyme genes in a bacterial metabolic network

    T2 - Reconstruction of the lysine-degradation pathway of Pseudomonas aeruginosa

    AU - Yamanishi, Yoshihiro

    AU - Mihara, Hisaaki

    AU - Osaki, Motoharu

    AU - Muramatsu, Hisashi

    AU - Esaki, Nobuyoshi

    AU - Sato, Tetsuya

    AU - Hizukuri, Yoshiyuki

    AU - Goto, Susumu

    AU - Kanehisa, Minoru

    PY - 2007/5/1

    Y1 - 2007/5/1

    N2 - The metabolic network is an important biological network which consists of enzymes and chemical compounds. However, a large number of metabolic pathways remains unknown, and most organism-specific metabolic pathways contain many missing enzymes. We present a novel method to identify the genes coding for missing enzymes using available genomic and chemical information from bacterial genomes. The proposed method consists of two steps: (a) estimation of the functional association between the genes with respect to chromosomal proximity and evolutionary association, using supervised network inference; and (b) selection of gene candidates for missing enzymes based on the original candidate score and the chemical reaction information encoded in the EC number. We applied the proposed methods to infer the metabolic network for the bacteria Pseudomonas aeruginosa from two genomic datasets: gene position and phylogenetic profiles. Next, we predicted several missing enzyme genes to reconstruct the lysine-degradation pathway in P. aeruginosa using EC number information. As a result, we identified PA0266 as a putative 5-aminovalerate aminotransferase (EC 2.6.1.48) and PA0265 as a putative glutarate semialdehyde dehydrogenase (EC 1.2.1.20). To verify our prediction, we conducted biochemical assays and examined the activity of the products of the predicted genes, PA0265 and PA0266, in a coupled reaction. We observed that the predicted gene products catalyzed the expected reactions; no activity was seen when both gene products were omitted from the reaction.

    AB - The metabolic network is an important biological network which consists of enzymes and chemical compounds. However, a large number of metabolic pathways remains unknown, and most organism-specific metabolic pathways contain many missing enzymes. We present a novel method to identify the genes coding for missing enzymes using available genomic and chemical information from bacterial genomes. The proposed method consists of two steps: (a) estimation of the functional association between the genes with respect to chromosomal proximity and evolutionary association, using supervised network inference; and (b) selection of gene candidates for missing enzymes based on the original candidate score and the chemical reaction information encoded in the EC number. We applied the proposed methods to infer the metabolic network for the bacteria Pseudomonas aeruginosa from two genomic datasets: gene position and phylogenetic profiles. Next, we predicted several missing enzyme genes to reconstruct the lysine-degradation pathway in P. aeruginosa using EC number information. As a result, we identified PA0266 as a putative 5-aminovalerate aminotransferase (EC 2.6.1.48) and PA0265 as a putative glutarate semialdehyde dehydrogenase (EC 1.2.1.20). To verify our prediction, we conducted biochemical assays and examined the activity of the products of the predicted genes, PA0265 and PA0266, in a coupled reaction. We observed that the predicted gene products catalyzed the expected reactions; no activity was seen when both gene products were omitted from the reaction.

    UR - http://www.scopus.com/inward/record.url?scp=34247374704&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=34247374704&partnerID=8YFLogxK

    U2 - 10.1111/j.1742-4658.2007.05763.x

    DO - 10.1111/j.1742-4658.2007.05763.x

    M3 - Article

    C2 - 17388807

    AN - SCOPUS:34247374704

    VL - 274

    SP - 2262

    EP - 2273

    JO - FEBS Journal

    JF - FEBS Journal

    SN - 1742-464X

    IS - 9

    ER -