Multifunctional enzymes and evolution of biosynthetic pathways: retro-evolution by jumps

Proteins. 1999 Nov 1;37(2):303-9. doi: 10.1002/(sici)1097-0134(19991101)37:2<303::aid-prot15>;2-6.


A likely scenario of evolution of biosynthetic pathways is believed to have occurred by retro-evolution through recruitment of existing enzymes rather than generation of de novo classes. It had been proposed that such retro-evolution occurred in steps as a response to depletion of an essential metabolite and availability of another related substance in the environment. In this article, I argue that because of instability of many such extant intermediates, it is unlikely that retro-evolution had occurred in steps. I further propose that such evolution in many cases has taken place by jumps, i.e., by recruitment of a multifunctional enzyme capable of catalyzing several steps at a time, albeit inefficiently. I further speculate that in some cases one primordial multienzyme may have catalyzed the whole sequence of reaction of a biosynthetic pathway, i.e., the pathway may have evolved by a single leap. Gene duplications and further evolution to more efficient enzymes led to extant pathways. Such a mechanism predicts that some or all enzymes of a pathway must have descended from a common ancestor. Sequence and structural homologies among extant enzymes of a biosynthetic pathway have been examined.

MeSH terms

  • Amino Acids / biosynthesis
  • Bacteria / enzymology
  • Bacteria / metabolism
  • Catalysis
  • Diaminopimelic Acid / metabolism
  • Enzymes / biosynthesis*
  • Enzymes / chemistry
  • Evolution, Molecular*
  • Methionine / biosynthesis
  • Models, Biological
  • Models, Molecular
  • Protein Structure, Tertiary
  • Purines / biosynthesis


  • Amino Acids
  • Enzymes
  • Purines
  • Diaminopimelic Acid
  • Methionine
  • purine