Identifying the missing steps of the autotrophic 3-hydroxypropionate CO2 fixation cycle in Chloroflexus aurantiacus

Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21317-22. doi: 10.1073/pnas.0908356106. Epub 2009 Dec 2.


The phototrophic bacterium Chloroflexus aurantiacus uses a yet unsolved 3-hydroxypropionate cycle for autotrophic CO(2) fixation. It starts from acetyl-CoA, with acetyl-CoA and propionyl-CoA carboxylases acting as carboxylating enzymes. In a first cycle, (S)-malyl-CoA is formed from acetyl-CoA and 2 molecules of bicarbonate. (S)-Malyl-CoA cleavage releases the CO(2) fixation product glyoxylate and regenerates the starting molecule acetyl-CoA. Here we complete the missing steps devoted to glyoxylate assimilation. In a second cycle, glyoxylate is combined with propionyl-CoA, an intermediate of the first cycle, to form beta-methylmalyl-CoA. This condensation is followed by dehydration to mesaconyl-C1-CoA. An unprecedented CoA transferase catalyzes the intramolecular transfer of the CoA moiety to the C4 carboxyl group of mesaconate. Mesaconyl-C4-CoA then is hydrated by an enoyl-CoA hydratase to (S)-citramalyl-CoA. (S)-Citramalyl-CoA is cleaved into acetyl-CoA and pyruvate by a tri-functional lyase, which previously cleaved (S)-malyl-CoA and formed beta-methylmalyl-CoA. Thus, the enigmatic disproportionation of glyoxylate and propionyl-CoA into acetyl-CoA and pyruvate is solved in an elegant and economic way requiring only 3 additional enzymes. The whole bicyclic pathway results in pyruvate formation from 3 molecules of bicarbonate and involves 19 steps but only 13 enzymes. Elements of the 3-hydroxypropionate cycle may be used for the assimilation of small organic molecules. The 3-hydroxypropionate cycle is compared with the Calvin-Benson-Bassham cycle and other autotrophic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acetyl-CoA Carboxylase / metabolism
  • Acyl Coenzyme A / metabolism
  • Autotrophic Processes*
  • Carbon Dioxide / metabolism*
  • Chloroflexus / metabolism*
  • Glyoxylates / metabolism
  • Lactic Acid / analogs & derivatives*
  • Lactic Acid / metabolism
  • Metabolic Networks and Pathways*
  • Methylmalonyl-CoA Decarboxylase / metabolism


  • Acyl Coenzyme A
  • Glyoxylates
  • Carbon Dioxide
  • propionyl-coenzyme A
  • Lactic Acid
  • Acetyl Coenzyme A
  • hydracrylic acid
  • Acetyl-CoA Carboxylase
  • Methylmalonyl-CoA Decarboxylase
  • glyoxylic acid