2009 Masaaki Kotera kot@kuicr.kyoto-u.ac.jp
2
I II / A () B1 () B2 B12 C () D A D
() () () () DNA 5-
http://www.genome.jp/kegg/pathway.html KEGG PATHWAY Database
Xenobiotics biodegradation
http://www.genome.jp/kegg/pathway.html KEGG PATHWAY Database
Human Diseases
Type I diabetes
H00069
New Page
P450 O-, N-, S- UDP- N - -S- N-
http://www.genome.jp/kegg/pathway.html KEGG PATHWAY Database
Xenobiotics biodegradation
Drug metabolism
http://www.genome.jp/kegg/pathway.html KEGG PATHWAY Database
Secondary metabolites
(small world)
EC
Jeong et al. Jeong et al., The large-scale organization of metabolic networks, Nature 407, 651-654 (2000).
Arita Arita, The metabolic world of Escherichia coli is not small, Proc Natl Acad Sci U S A. 101(6): 1543 1547 (2004).
Arita Arita, The metabolic world of Escherichia coli is not small, Proc Natl Acad Sci U S A. 101(6): 1543 1547 (2004).
Reactant pairs (RPAIRs) AH 2 + B = A + BH 2 AH 2 A AB + C = A + BC AB A B BH 2 C BC AB + H 2 O = AH + BOH AB AH AB = A + B AB A H 2 O BOH B Kotera et al., Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions J. Am. Chem. Soc. 126, 16487-16498 (2004).
Atom alignment of the molecular graphs O6a O6a O6a O6a C6a C6a C5a O5a O5a C5a C1b C1a C1c O1a C1a Hattori et al., Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways J. Am. Chem. Soc. 125, 11853-11865 (2003).
RPAIR database 5,669 5,327 -
Faust et al Faust et al., Metabolic pathfinding using RPAIR annotation J Mol Biol. 388(2):390-414 (2009).
Moriya et al Moriya et al., KAAS: an automatic genome annotation and pathway reconstruction server, Nucleic Acids Research 35, W182-W185 (2007).
Yamanishi et al Yamanishi et al., Prediction of missing enzyme genes in a bacterial metabolic network, FEBS Journal, 274 (9), 2262-2273 (2007).
Yamanishi et al Yamanishi et al., Prediction of missing enzyme genes in a bacterial metabolic network, FEBS Journal, 274 (9), 2262-2273 (2007).
RDM Atom alignment of the molecular graphs O6a C6a O6a O6a O6a C6a Matched subgraph C5a O5a O5a C5a R D M C1b C1c C5a C1a * C1c C5a C1b C1c C1a Reaction center O1a Differences C1a Kotera et al., Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions J. Am. Chem. Soc, 126, 16487-16498 (2004).
E-zyme chemical annotation RPAIR database RDM RDM R D M C1b C1c C5a C1a * C1c C5a! Yamanishi et al., E-zyme: predicting potential EC numbers from the chemical transformation pattern of substrate-product pairs Bioinformatics, 25(12) i179-i186 (2009).
Oh et al Oh et al., Systematic Analysis of Enzyme- Catalyzed Reaction Patterns and Prediction of Microbial Biodegradation Pathways, J Chem Inf Model 47, 1702-12 (2007).
Fenner et al Fenner et al. Data-driven extraction of relative reasoning rules to limit combinatorial explosion in biodegradation pathway prediction, Bioinformatics 24 (18): 2079-2085 (2008).
Kotera et al Kotera et al., Eliciting possible reaction equations and metabolic pathways involving orphan metabolites, J Chem Inf Model. 48(12): 2335-2349 (2008).
G E R #1 G E R #2 Genome annotation G E R G E R Chemical annotation
EC EC EC EC
1. oxidoreductases 2. transferases 3. hydrolases 4. lyases 5. Isomerases 6. ligases EC Class Subclass Sub-subclass Complete EC number 1.1 1.2 1.3 1.4 1.5 : : 1.3.1 1.3.2 1.3.3 1.3.5 : : 1.3.1.1 1.3.1.2 1.3.1.3 : : 1.3.1.69 zeatin reductase : :
EC EC EC EC 1. 2. 3. 4. 5. RS EZ 6.
EC Kotera et al., Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions J. Am. Chem. Soc, 126, 16487-16498 (2004).
Thioesterase domain of polypeptide, polyketide and fatty acid synthases SCOPEC Aspartate aminotransferaselike domain NAD(P)-binding Rossmann-fold domain Phosphotransferases on alcohol groups Hydro-lyase Alkyl or aryl transferase P-loop containing nucleoside triphosphate hydrolases (Trans)glycosidases Alcohol dehydrogenase using NAD(P)+ Trypsin-like serine proteases O- or S-glycosidases George et al., SCOPEC: a database of protein catalytic domains, Bioinformatics, 20, i130-i136 (2004).
P450 40% 55% CYP3A4 33 3A3A 4 EC 1.14
EC 2.4 Ross et al., Higher plant glycosyltransferases, Genome Biol. 2(2): reviews3004.1 reviews3004.6 (2001).
EC EC EC EC
PubMed kyomu@bic.kyoto-u.ac.jp 20091123