Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Mar 25;53(3):613-22.
doi: 10.1021/ci3005379. Epub 2013 Feb 19.

Modular architecture of metabolic pathways revealed by conserved sequences of reactions

Ai Muto  1 , Masaaki Kotera, Toshiaki Tokimatsu, Zenichi Nakagawa, Susumu Goto, Minoru Kanehisa
Affiliations
Free PMC article

Modular architecture of metabolic pathways revealed by conserved sequences of reactions

Ai Muto et al. J Chem Inf Model. .
Free PMC article

Abstract

The metabolic network is both a network of chemical reactions and a network of enzymes that catalyze reactions. Toward better understanding of this duality in the evolution of the metabolic network, we developed a method to extract conserved sequences of reactions called reaction modules from the analysis of chemical compound structure transformation patterns in all known metabolic pathways stored in the KEGG PATHWAY database. The extracted reaction modules are repeatedly used as if they are building blocks of the metabolic network and contain chemical logic of organic reactions. Furthermore, the reaction modules often correspond to traditional pathway modules defined as sets of enzymes in the KEGG MODULE database and sometimes to operon-like gene clusters in prokaryotic genomes. We identified well-conserved, possibly ancient, reaction modules involving 2-oxocarboxylic acids. The chain extension module that appears as the tricarboxylic acid (TCA) reaction sequence in the TCA cycle is now shown to be used in other pathways together with different types of modification modules. We also identified reaction modules and their connection patterns for aromatic ring cleavages in microbial biodegradation pathways, which are most characteristic in terms of both distinct reaction sequences and distinct gene clusters. The modular architecture of biodegradation modules will have a potential for predicting degradation pathways of xenobiotic compounds. The collection of these and many other reaction modules is made available as part of the KEGG database.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Fingerprint representation of the RDM pattern. Two reaction class entries RC00106 and RC01192 are shown for the reactant pairs of pyruvate and acetolactate (upper) and oxobutanoate and 2-aceto-2-hydroxybutanoate (lower). The RDM notation for these reaction class entries is converted to the fingerprint representation, which reveals that they are the same in the fingerprint representation despite the difference in the M atom (circled) in the RDM notation.
Figure 2
Figure 2
Architecture of reaction modules consisting of 2-oxocarboxylic acid chain extension and modification, generating (A) basic amino acids and (B) branched-chain amino acids. Vertical arrows indicate the extension modules RM001. Horizontal arrows indicate the modification modules RM002, RM032, and RM033 together with the reductive amination step (RC00006 and RC00036).
Figure 3
Figure 3
Aromatic ring cleavage modules in microbial degradation pathways. Aromatic rings are cleaved in the following three steps. The first step is an occasional preprocessing step (RM003) converting a methyl group into a carboxylic group on the aromatic ring. The second step is the main step of dihydroxylation, which is classified into three types (RM006, RM004, and RM005) depending on how two hydroxyl groups are added on the aromatic ring. The third step is either ortho-cleavage (RM008) or meta-cleavage (RM009) followed by characteristic reaction patterns leading to TCA cycle intermediates.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bono H.; Ogata H.; Goto S.; Kanehisa M. Reconstruction of amino acid biosynthesis pathways from the complete genome sequence. Genome Res. 1998, 8, 203–210. - PubMed
    1. Galperin M. Y.; Koonin E. V. Functional genomics and enzyme evolution. Homologous and analogous enzymes encoded in microbial genomes. Genetica 1999, 106, 159–170. - PubMed
    1. Dandekar T.; Schuster S.; Snel B.; Huynen M.; Bork P. Pathway alignment: application to the comparative analysis of glycolytic enzymes. Biochem. J. 1999, 343, 115–124. - PMC - PubMed
    1. Forst C. V.; Schulten K. Evolution of metabolisms: a new method for the comparison of metabolic pathways using genomics information. J. Comput. Biol. 1999, 6, 343–360. - PubMed
    1. Ogata H.; Fujibuchi W.; Goto S.; Kanehisa M. A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters. Nucleic Acids Res. 2000, 28, 4021–4028. - PMC - PubMed

Publication types

LinkOut - more resources