Pathway Evolution, Structurally Speaking

Curr Opin Struct Biol. 2002 Jun;12(3):374-82. doi: 10.1016/s0959-440x(02)00331-7.


Small-molecule metabolism forms the core of the metabolic processes of all living organisms. As early as 1945, possible mechanisms for the evolution of such a complex metabolic system were considered. The problem is to explain the appearance and development of a highly regulated complex network of interacting proteins and substrates from a limited structural and functional repertoire. By permitting the co-analysis of phylogeny and metabolism, the combined exploitation of pathway and structural databases, as well as the use of multiple-sequence alignment search algorithms, sheds light on this problem. Much of the current research suggests a chemistry-driven 'patchwork' model of pathway evolution, but other mechanisms may play a role. In the future, as metabolic structure and sequence space are further explored, it should become easier to trace the finer details of pathway development and understand how complexity has evolved.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Biological Evolution*
  • Enzymes / chemistry
  • Enzymes / metabolism
  • Escherichia coli / metabolism
  • Metabolism*
  • Protein Structure, Tertiary
  • Sequence Homology


  • Enzymes