The Crabtree effect, named after the English biochemist Herbert Grace Crabtree,[1] describes the phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol (alcohol) in aerobic conditions at high external glucose concentrations rather than producing biomass via the tricarboxylic acid (TCA) cycle, the usual process occurring aerobically in most yeasts e.g. Kluyveromyces spp.[2] This phenomenon is observed in most species of the Saccharomyces, Schizosaccharomyces, Debaryomyces, Brettanomyces, Torulopsis, Nematospora, and Nadsonia genera.[3] Increasing concentrations of glucose accelerates glycolysis (the breakdown of glucose) which results in the production of appreciable amounts of ATP through substrate-level phosphorylation. This reduces the need of oxidative phosphorylation done by the TCA cycle via the electron transport chain and therefore decreases oxygen consumption. The phenomenon is believed to have evolved as a competition mechanism (due to the antiseptic nature of ethanol) around the time when the first fruits on Earth fell from the trees.[2] The Crabtree effect works by repressing respiration by the fermentation pathway, dependent on the substrate.[4]

Ethanol formation in Crabtree-positive yeasts under strictly aerobic conditions was firstly thought to be caused by the inability of these organisms to increase the rate of respiration above a certain value. This critical value, above which alcoholic fermentation occurs, is dependent on the strain and the culture conditions.[5] More recent evidences demonstrated that the occurrence of alcoholic fermentation might not be primarily due to a limited respiratory capacity,[6] but could be caused by a limit in the cellular Gibbs energy dissipation rate.[7]

For S. cerevisiae in aerobic conditions,[8] glucose concentrations below 150 mg/L did not result in ethanol production. Above this value, ethanol was formed with rates increasing up to a glucose concentration of 1000 mg/L. Thus, above 150 mg/L glucose the organism exhibited a Crabtree effect.[9]

It was the study of tumor cells that led to the discovery of the Crabtree effect.[10] Tumor cells have a similar metabolism, the Warburg effect, in which they favor glycolysis over the oxidative phosphorylation pathway.[11]

References

  1. ^ Crabtree, HG (1929). "Observations on the carbohydrate metabolism of tumours". The Biochemical Journal. 23 (3): 536–45. doi:10.1042/bj0230536. PMC 1254097. PMID 16744238.
  2. ^ a b Thomson JM, Gaucher EA, Burgan MF, De Kee DW, Li T, Aris JP, Benner SA (2005). "Resurrecting ancestral alcohol dehydrogenases from yeast". Nat. Genet. 37 (6): 630–635. doi:10.1038/ng1553. PMC 3618678. PMID 15864308.
  3. ^ De Deken, R. H. (1966). "The Crabtree Effect: A Regulatory System in Yeast". J. Gen. Microbiol. 44 (2): 149–56. doi:10.1099/00221287-44-2-149. PMID 5969497.
  4. ^ De Deken, R. H. (1 August 1966). "The Crabtree Effect and its Relation to the Petite Mutation". Journal of General Microbiology. 44 (2): 157–165. doi:10.1099/00221287-44-2-157. PMID 5969498.
  5. ^ van Dijken and Scheffers, 1986 J.P. van Dijken, W.A. Scheffers; Redox balances in the metabolism of sugars by yeasts; FEMS Microbiol. Lett., 32 (3) (1986), pp. 199-224; https://doi.org/10.1016/0378-1097(86)90291-0
  6. ^ Postma, E; Verduyn, C; Scheffers, WA; Van Dijken, JP (February 1989). "Enzymic analysis of the crabtree effect in glucose-limited chemostat cultures of Saccharomyces cerevisiae". Applied and Environmental Microbiology. 55 (2): 468–77. Bibcode:1989ApEnM..55..468P. doi:10.1128/AEM.55.2.468-477.1989. PMC 184133. PMID 2566299.
  7. ^ Heinemann, Matthias; Leupold, Simeon; Niebel, Bastian (January 2019). "An upper limit on Gibbs energy dissipation governs cellular metabolism" (PDF). Nature Metabolism. 1 (1): 125–132. doi:10.1038/s42255-018-0006-7. ISSN 2522-5812. PMID 32694810. S2CID 104433703.
  8. ^ Verduyn, C., Zomerdijk, T.P.L., van Dijken, J.P. et al. Continuous measurement of ethanol production by aerobic yeast suspensions with an enzyme electrode. Appl Microbiol Biotechnol 19, 181–185 (1984). https://doi.org/10.1007/BF00256451
  9. ^ Verduyn, C., Zomerdijk, T.P.L., van Dijken, J.P. et al. Continuous measurement of ethanol production by aerobic yeast suspensions with an enzyme electrode. Appl Microbiol Biotechnol 19, 181–185 (1984). https://doi.org/10.1007/BF00256451
  10. ^ Pfeiffer, T; Morley, A (2014). "An evolutionary perspective on the Crabtree effect". Frontiers in Molecular Biosciences. 1: 17. doi:10.3389/fmolb.2014.00017. PMC 4429655. PMID 25988158.
  11. ^ Diaz-Ruiz, Rodrigo; Rigoulet, Michel; Devin, Anne (June 2011). "The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1807 (6): 568–576. doi:10.1016/j.bbabio.2010.08.010. PMID 20804724.

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