Functional versatility and molecular diversity of the metabolic map of Escherichia coli.

We have analyzed the known metabolic enzymes of Escherichia coli in relation to their biochemical reaction properties and their involvement in biochemical pathways. All enzymes involved in small-molecule metabolism and their corresponding protein sequences have been extracted from the EcoCyc database. These 548 metabolic enzymes are clustered into 405 protein families according to sequence similarity. In this study, we examine the functional versatility within enzyme families in terms of their reaction capabilities and pathway participation. In addition, we examine the molecular diversity of reactions and pathways according to their presence across enzyme families. These complex, many-to-many relationships between protein sequence and biochemical function reveal a significant degree of correlation between enzyme families and reactions. Pathways, however, appear to require more than one enzyme type to perform their complex biochemical transformations. Finally, the distribution of enzyme family members across different pathways provides support for the "recruitment" hypothesis of biochemical pathway evolution.

[1]  W. Gu,et al.  Evolutionary recruitment of biochemically specialized subdivisions of Family I within the protein superfamily of aminotransferases , 1996, Journal of bacteriology.

[2]  M. Gerstein,et al.  The relationship between protein structure and function: a comprehensive survey with application to the yeast genome. , 1999, Journal of molecular biology.

[3]  J. M. Wood,et al.  Sequence analysis identifies the proline dehydrogenase and delta 1-pyrroline-5-carboxylate dehydrogenase domains of the multifunctional Escherichia coli PutA protein. , 1994, Journal of molecular biology.

[4]  P D Karp,et al.  What we do not know about sequence analysis and sequence databases. , 1998, Bioinformatics.

[5]  Chris Sander,et al.  CAST: an iterative algorithm for the complexity analysis of sequence tracts , 2000, Bioinform..

[6]  Patricia C Babbitt,et al.  Can sequence determine function? , 2000, Genome Biology.

[7]  Sophia Tsoka,et al.  Prediction of protein interactions: metabolic enzymes are frequently involved in gene fusion , 2000, Nature Genetics.

[8]  M. Riley,et al.  Gene products of Escherichia coli: sequence comparisons and common ancestries. , 1995, Molecular biology and evolution.

[9]  M. Riley,et al.  Functions of the gene products of Escherichia coli , 1993, Microbiological reviews.

[10]  Anton J. Enright,et al.  GeneRAGE: a robust algorithm for sequence clustering and domain detection , 2000, Bioinform..

[11]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[12]  G. Petsko,et al.  On the origin of enzymatic species. , 1993, Trends in biochemical sciences.

[13]  T. Onasch,et al.  Importance of historical contingency in the stereochemistry of hydratase-dehydratase enzymes. , 1995, Science.

[14]  J. McCord.  Iron- and manganese-containing superoxide dismutases: structure, distribution, and evolutionary relationships. , 1976, Advances in experimental medicine and biology.

[15]  M S Waterman,et al.  Identification of common molecular subsequences. , 1981, Journal of molecular biology.

[16]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[17]  Peter D. Karp,et al.  The EcoCyc and MetaCyc databases , 2000, Nucleic Acids Res..

[18]  M. Gerstein,et al.  Assessing annotation transfer for genomics: quantifying the relations between protein sequence, structure and function through traditional and probabilistic scores. , 2000, Journal of molecular biology.

[19]  N H Horowitz,et al.  On the Evolution of Biochemical Syntheses. , 1945, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Sander,et al.  Genome sequences and great expectations , 2000, Genome Biology.

[21]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[22]  R. Jensen.  Enzyme recruitment in evolution of new function. , 1976, Annual review of microbiology.

[23]  P. Bork,et al.  Homology among (betaalpha)(8) barrels: implications for the evolution of metabolic pathways. , 2000, Journal of molecular biology.

[24]  Peter D. Karp,et al.  Prediction of Enzyme Classification from Protein Sequence without the Use of Sequence Similarity , 1997, ISMB.

[25]  Amos Bairoch,et al.  The ENZYME database in 2000 , 2000, Nucleic Acids Res..

[26]  Tim J. P. Hubbard,et al.  SCOP: a structural classification of proteins database , 1998, Nucleic Acids Res..

[27]  P D Karp,et al.  Global properties of the metabolic map of Escherichia coli. , 2000, Genome research.