Crabtree effect

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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 is not 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]

Related Research Articles

Glycolysis Metabolic pathway

Glycolysis is the metabolic pathway that converts glucose, into pyruvic acid. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

Yeast Informal group of fungi

Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitute 1% of all described fungal species.

Phosphorylation Chemical process of introducing a phosphate

In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process are common in biology. Protein phosphorylation often activates many enzymes.

Cellular respiration Process to convert glucose to ATP in cells

Cellular respiration is a set of metabolic reactions and processes that take place in the cells of organisms to convert chemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. The reactions involved in respiration are catabolic reactions, which break large molecules into smaller ones, releasing energy. Respiration is one of the key ways a cell releases chemical energy to fuel cellular activity. The overall reaction occurs in a series of biochemical steps, some of which are redox reactions. Although cellular respiration is technically a combustion reaction, it is an unusual one because of the slow, controlled release of energy from the series of reactions.

Syrup Thick, viscous solution of sugar in water

In cooking, a syrup is a condiment that is a thick, viscous liquid consisting primarily of a solution of sugar in water, containing a large amount of dissolved sugars but showing little tendency to deposit crystals. Its consistency is similar to that of molasses. The viscosity arises from the multiple hydrogen bonds between the dissolved sugar, which has many hydroxyl (OH) groups.

Fusel alcohols or fuselol, also sometimes called fusel oils in Europe, are mixtures of several higher alcohols produced as a by-product of alcoholic fermentation. The word Fusel[ˈfuːzl̩] is German for "bad liquor".

Ethanol fermentation Biological process that produces ethanol and carbon dioxide as by-products

Ethanol fermentation, also called alcoholic fermentation, is a biological process which converts sugars such as glucose, fructose, and sucrose into cellular energy, producing ethanol and carbon dioxide as by-products. Because yeasts perform this conversion in the absence of oxygen, alcoholic fermentation is considered an anaerobic process. It also takes place in some species of fish where it provides energy when oxygen is scarce.

In oncology, the Warburg effect is the observation that most cancer cells produce energy predominantly not through the 'usual' citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not the mitochondria, even in the presence of abundant oxygen. This observation was first published by Otto Heinrich Warburg, who was awarded the 1931 Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme". The precise mechanism and therapeutic implications of the Warburg effect, however, remain unclear.

<i>Zygosaccharomyces bailii</i> Species of fungus

Zygosaccharomyces bailii is a species in the genus Zygosaccharomyces. It was initially described as Saccharomyces bailii by Lindner in 1895, but in 1983 it was reclassified as Zygosaccharomyces bailii in the work by Barnett et al.

Fermentation Metabolic process

Fermentation is a metabolic process that produces chemical changes in organic substrates through the action of enzymes. In biochemistry, it is narrowly defined as the extraction of energy from carbohydrates in the absence of oxygen. In food production, it may more broadly refer to any process in which the activity of microorganisms brings about a desirable change to a foodstuff or beverage. The science of fermentation is known as zymology.

Zymomonas mobilis is a Gram negative, facultative anaerobic, non-sporulating, polarly-flagellated, rod-shaped bacterium. It is the only species found in the genus Zymomonas. It has notable bioethanol-producing capabilities, which surpass yeast in some aspects. It was originally isolated from alcoholic beverages like the African palm wine, the Mexican pulque, and also as a contaminant of cider and beer in European countries.

<i>Kluyveromyces marxianus</i> Species of fungus

Kluyveromyces marxianus in ascomycetous yeast and member of the genus, Kluyveromyces. It is the sexual stage of Atelosaccharomyces pseudotropicalis also known as Candida kefyr. This species has a homothallic mating system and is often isolated from dairy products.

The Pasteur effect is an inhibiting effect of oxygen on the fermentation process. It is a sudden change from anaerobic to aerobic metabolism.

Fed-batch culture is, in the broadest sense, defined as an operational technique in biotechnological processes where one or more nutrients (substrates) are fed (supplied) to the bioreactor during cultivation and in which the product(s) remain in the bioreactor until the end of the run. An alternative description of the method is that of a culture in which "a base medium supports initial cell culture and a feed medium is added to prevent nutrient depletion". It is also a type of semi-batch culture. In some cases, all the nutrients are fed into the bioreactor. The advantage of the fed-batch culture is that one can control concentration of fed-substrate in the culture liquid at arbitrarily desired levels.

SCOBY Symbiotic culture of bacteria and yeast

SCOBY is the commonly used acronym for "symbiotic culture of bacteria and yeast", and is formed after the completion of a unique symbiotic fermentation process of lactic acid bacteria (LAB), acetic acid bacteria (AAB), and yeast to form several sour foods and beverages such as kombucha and kimchi. Beer and wine also undergo fermentation with yeast, but the lactic acid bacteria and acetic acid bacteria components unique to SCOBY are usually viewed as a source of spoilage rather than a desired addition. Both LAB and AAB enter on the surface of barley and malt in beer fermentation and grapes in wine fermentation; LAB lower the pH of the beer while AAB take the ethanol produced from the yeast and oxidize it further into vinegar, resulting in a sour taste and smell. AAB are also responsible for the formation of the cellulose SCOBY.

Xylose metabolism

D-Xylose is a five-carbon aldose that can be catabolized or metabolized into useful products by a variety of organisms.

Auto-brewery syndrome Medical condition

Auto-brewery syndrome(ABS) is a condition characterized by the fermentation of ingested carbohydrates in the gastrointestinal tract of the body caused by bacteria or fungi. ABS is a rare medical condition in which intoxicating quantities of ethanol are produced through endogenous fermentation within the digestive system. The organisms responsible for ABS include various yeasts and bacteria, including Saccharomyces cerevisiae, S. boulardii, Candida albicans, C. tropicalis, C. krusei, C. glabrata, C. kefyr, C. parapsilosis, Klebsiella pneumoniae, and Enterococcus faecium. These organisms use lactic acid fermentation or mixed acid fermentation pathways to produce an ethanol end product. The ethanol generated from these pathways is absorbed in the small intestine, causing an increase in blood alcohol concentrations that produce the effects of intoxication without the consumption of alcohol.

Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate instead of using the respiratory pathway, even in the presence of oxygen. As a result of employing this metabolic strategy, cells excrete metabolites like lactate, acetate and ethanol. Incomplete oxidation of growth substrates yields less energy than complete oxidation through respiration, and yet overflow metabolism - known as the Warburg effect in the context of cancer and the Crabtree effect in the context of yeast - occurs ubiquitously among fast-growing cells, including bacteria, fungi and mammalian cells.

Aerobic fermentation or aerobic glycolysis is a metabolic process by which cells metabolize sugars via fermentation in the presence of oxygen and occurs through the repression of normal respiratory metabolism. It is referred to as the Crabtree effect in yeast. and is part of the Warburg effect in tumor cells. While aerobic fermentation does not produce adenosine triphosphate (ATP) in high yield, it allows proliferating cells to convert nutrients such as glucose and glutamine more efficiently into biomass by avoiding unnecessary catabolic oxidation of such nutrients into carbon dioxide, preserving carbon-carbon bonds and promoting anabolism.

Metschnikowia pulcherrima is a ubiquitous species of yeast, with numerous strains, belonging to the family Metschnikowiaceae, and found on grapes, cherries, flowers, spoiled fruit and consequently carried by fruit flies. It is a non-Saccharomyces yeast and plays an important role in the vinification of wine when it is present on grapes or winery equipment, and has historically seen use in South Africa’s wine industry. It is also being studied at the University of Bath as a possible alternative to the use of Palm oil, and early results show promise. M. pulcherrima is ovoid to ellipsoidal in shape and reproduces by budding. Its cells are globose and thick-walled, holding a single, large oil droplet of high refractive index. As the result of incomplete budding where cells remain attached after division, pseudohyphae may form under anaerobic conditions.

References

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  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.
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  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.
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  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.
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