Small-molecule Metabolism: An Enzyme Mosaic

Trends Biotechnol. 2001 Dec;19(12):482-6. doi: 10.1016/s0167-7799(01)01813-3.


Escherichia coli has been a popular organism for studying metabolic pathways. In an attempt to find out more about how these pathways are constructed, the enzymes were analysed by defining their protein domains. Structural assignments and sequence comparisons were used to show that 213 domain families constitute approximately 90% of the enzymes in the small-molecule metabolic pathways. Catalytic or cofactor-binding properties between family members are often conserved, while recognition of the main substrate with change in catalytic mechanism is only observed in a few cases of consecutive enzymes in a pathway. Recruitment of domains across pathways is very common, but there is little regularity in the pattern of domains in metabolic pathways. This is analogous to a mosaic in which a stone of a certain colour is selected to fill a position in the picture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites / physiology
  • Coenzymes / metabolism
  • Enzymes / chemistry*
  • Enzymes / metabolism*
  • Escherichia coli / enzymology*
  • Escherichia coli / metabolism
  • Evolution, Molecular
  • Fucose / metabolism
  • Nucleosides / metabolism
  • Nucleotides / metabolism
  • Protein Structure, Tertiary / physiology
  • Purines / biosynthesis
  • Pyrimidines / biosynthesis
  • Pyruvic Acid / metabolism
  • Sequence Homology
  • Substrate Specificity / physiology
  • Tryptophan / biosynthesis


  • Coenzymes
  • Enzymes
  • Nucleosides
  • Nucleotides
  • Purines
  • Pyrimidines
  • Fucose
  • Pyruvic Acid
  • Tryptophan
  • pyrimidine
  • purine