Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to winemaking, baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes (one can see the yeast as a component of the thin white film on the skins of some dark-colored fruits such as plums; it exists among the waxes of the cuticle). It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model bacterium. It is the microorganism behind the most common type of fermentation. S. cerevisiae cells are round to ovoid, 5–10 micrometres in diameter. It reproduces by a division process known as budding.^[1]

Many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes.

Saccharomyces cerevisiae is currently the only yeast cell that is known to have Berkeley bodies present, which are involved in particular secretory pathways.

Antibodies against S. cerevisiae are found in 60–70% of patients with Crohn's disease and 10–15% of patients with ulcerative colitis (and 8% of healthy controls).^[2]

Nomenclature [edit]

"Saccharomyces" derives from Latinized Greek and means "sugar mold" or "sugar fungus", saccharo- being the combining form "sugar-" and myces being "fungus". Cerevisiae comes from Latin and means "of beer". Other names for the organism are:

• S. cerevisiae short form of the scientific name
• Brewer's yeast, though other species are also used in brewing
• Ale yeast
• Top-fermenting yeast
• Baker's yeast
• Budding yeast

This species is also the main source of nutritional yeast and yeast extract.

Biology [edit]

Ecology [edit]

In nature, yeast cells are found primarily on ripe fruits such as grapes (before maturation, grapes are almost free of yeasts). Since S. cerevisiae is not airborne, it requires a vector to move. In fact, queens of social wasps overwintering as adults (Vespa crabro and Polistes spp.) can harbor yeast cells from autumn to spring and transmit them to their progeny.^[3]

Life cycle [edit]

There are two forms in which yeast cells can survive and grow: haploid and diploid. The haploid cells undergo a simple life cycle of mitosis and growth, and under conditions of high stress will, in general, die. The diploid cells (the preferential 'form' of yeast) similarly undergo a simple life cycle of mitosis and growth, but under conditions of stress can undergo sporulation, entering meiosis and producing four haploid spores, which can proceed on to mate. With adequate nutrient, yeast cells can double in 100 minutes.^[4][5] Mean replicative lifespan is about 26 cell divisions.^[6][7]

Nutritional requirements [edit]

All strains of S. cerevisiae can grow aerobically on glucose, maltose, and trehalose and fail to grow on lactose and cellobiose. However, growth on other sugars is variable. Galactose and fructose are shown to be two of the best fermenting sugars. The ability of yeasts to use different sugars can differ depending on whether they are grown aerobically or anaerobically. Some strains cannot grow anaerobically on sucrose and trehalose.

All strains can use ammonia and urea as the sole nitrogen source, but cannot use nitrate, since they lack the ability to reduce them to ammonium ions. They can also use most amino acids, small peptides, and nitrogen bases as a nitrogen source. Histidine, glycine, cystine, and lysine are, however, not readily used. S. cerevisiae does not excrete proteases, so extracellular protein cannot be metabolized.

Yeasts also have a requirement for phosphorus, which is assimilated as a dihydrogen phosphate ion, and sulfur, which can be assimilated as a sulfate ion or as organic sulfur compounds such as the amino acids methionine and cysteine. Some metals, like magnesium, iron, calcium, and zinc, are also required for good growth of the yeast.

Mating [edit]

Yeast has two mating types, a and α (alpha), which show primitive aspects of sex differentiation.^[8] As in many other eukaryotes, mating serves the purpose of genetic recombination, i.e. to produce novel combinations of chromosomes. Two haploid yeast cells of opposite mating type can mate to form diploid cells which can either sporulate to form another generation of haploid cells or they can continue to exist as diploid cells. Mating has been exploited by biologists as a tool to combine genes, plasmids, or proteins at will, e.g. in yeast two-hybrid screens.

Cell cycle [edit]

Growth in yeast is synchronised with the growth of the bud, which reaches the size of the mature cell by the time it separates from the parent cell. In rapidly growing yeast cultures, all the cells can be seen to have buds, since bud formation occupies the whole cell cycle. Both mother and daughter cells can initiate bud formation before cell separation has occurred. In yeast cultures growing more slowly, cells lacking buds can be seen, and bud formation only occupies a part of the cell cycle. The cell cycle in yeast normally consists of the following stages – G1, S, G2, and M – which are the normal stages of the cell cycle. [edit]

Life cycle [edit]

Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to winemaking, baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes (one can see the yeast as a component of the thin white film on the skins of some dark-colored fruits such as plums; it exists among the waxes of the cuticle). It is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model bacterium. It is the microorganism behind the most common type of fermentation. S. cerevisiae cells are round to ovoid, 5–10 micrometres in diameter. It reproduces by a division process known as budding.[1] Many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. Saccharomyces cerevisiae is currently the only yeast cell that is known to have Berkeley bodies present, which are involved in particular secretory pathways. Antibodies against S. cerevisiae are found in 60–70% of patients with Crohn's disease and 10–15% of patients with ulcerative colitis (and 8% of healthy controls).[2] There are two forms in which yeast cells can survive and grow: haploid and diploid. The haploid cells undergo a simple life cycle of mitosis and growth, and under conditions of high stress will, in general, die. The diploid cells (the preferential 'form' of yeast) similarly undergo a simple life cycle of mitosis and growth, but under conditions of stress can undergo sporulation, entering meiosis and producing four haploid spores, which can proceed on to mate. With adequate nutrient, yeast cells can double in 100 minutes.[4][5] Mean replicative lifespan is about 26 cell divisions.[6][7]Brewing Saccharomyces cerevisiae is used in brewing beer, when it is sometimes called a top-fermenting or top-cropping yeast. It is so called because during the fermentation process its hydrophobic surface causes the flocs to adhere to CO2 and rise to the top of the fermentation vessel. Top-fermenting yeasts are fermented at higher temperatures than lager yeasts, and the resulting beers have a different flavor than the same beverage fermented with a lager yeast. "Fruity esters" may be formed if the yeast undergoes temperatures near 21 °C (70 °F), or if the fermentation temperature of the beverage fluctuates during the process. Lager yeast normally ferments at a temperature of approximately 5 °C (41 °F), where Saccharomyces cerevisiae becomes dormant. Lager yeast can be fermented at a higher temperature to create a beer style known as "steam beer".

Yeast in biological research [edit]

A model organism [edit]

Saccharomyces cerevisiae
Numbered ticks are 11 micrometres apart.

When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time, accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. The yeast species S. pombe and S. cerevisiae are both well studied; these two species diverged approximately 600 to 300 million years ago, and are significant tools in the study of DNA damage and repair mechanisms.^[9]

S. cerevisiae has developed as a model organism because it scores favorably on a number of these criteria.

• As a single celled organism S. cerevisiae is small with a short generation time (doubling time 1.25–2 hours^[10] at 30 °C or 86 °F) and can be easily cultured. These are all positive characteristics in that they allow for the swift production and maintenance of multiple specimen lines at low cost.
• S. cerevisiae can be transformed allowing for either the addition of new genes or deletion through homologous recombination. Furthermore, the ability to grow S. cerevisiae as a haploid simplifies the creation of gene knockouts strains.
• As a eukaryote, S. cerevisiae shares the complex internal cell structure of plants and animals without the high percentage of non-coding DNA that can confound research in higher eukaryotes.
• S. cerevisiae research is a strong economic driver, at least initially, as a result of its established use in industry.

Yeast in the study of aging [edit]

S. cerevisiae has been highly studied as a model organism to better understand aging for more than five decades and has contributed to the identification of more mammalian genes affecting aging than any other model organism.^[11] Some of the topics studied using yeast are calorie restriction, as well as in genes and cellular pathways involved in senescence. The two most common methods of measuring aging in yeast are Replicative Life Span, which measured the amount of times a cell divides, and Chronological Life Span, which measures how long a cell can survive in a non-dividing stasis state.^[11] Limiting the amount of glucose or amino acids in the growth medium has been shown to increase RLS and CLS in yeast as well as other organisms and is referred to as Calorie Restriction or Dietary Restriction.^[12] Initially this was thought to increase RLS by up-regulating the sir2 enzyme, however it was later discovered that this effect is independent of sir2. Over-expression of the genes sir2 and fob1 has been shown to increase RLS by preventing the accumulation of extrachromosomal rDNA circles, which are thought to be one of the causes of senescence in yeast.^[12] The effects of DR may be the result of a decreased signaling in the TOR cellular pathway.^[11] This pathway modulates the cell's response to nutrients and mutations that decrease TOR activity were found to increase CLS and RLS.^[11][12] This has also been shown to be the case in other animals.^[11][12] A yeast mutant lacking the genes sch9 and ras2 have recently been shown to have a tenfold increase in chronological life span under conditions of calorie restriction and is the largest increase achieved in any organism.^[13][14]

S. cerevisiae contain prions and scientists do not yet know whether they play a role in prion disease, although they have found that nonpathogenic prions can be converted to pathogenic forms. They do not know yet how this happens.

Genome sequencing [edit]

S. cerevisiae was the first eukaryotic genome that was completely sequenced.^[15] The genome sequence was released in the public domain on April 24, 1996. Since then, regular updates have been maintained at the Saccharomyces Genome Database. This database is a highly annotated and cross-referenced database for yeast researchers. Another important S. cerevisiae database is maintained by the Munich Information Center for Protein Sequences (MIPS). The genome is composed of about 12,156,677 base pairs and 6,275 genes, compactly organized on 16 chromosomes. Only about 5,800 of these are believed to be true functional genes. Yeast is estimated to share at least 31% of its genome with that of humans.^[16] Yeast genes are classified using gene symbols (such as sch9) or systematic names. Each of the 16 chromosomes of yeast are represented by letters A-P, and the gene is further classified by which side of the centromere, the location and which strand of double-stranded DNA where it is present.^{[citation needed]}

Yeast gene function and interactions [edit]

The availability of the S. cerevisiae genome sequence and a set of deletion mutants covering 90% of the yeast genome^[17] has further enhanced the power of S. cerevisiae as a model for understanding the regulation of eukaryotic cells. A project underway to analyze the genetic interactions of all double deletion mutants through synthetic genetic array analysis will take this research one step further. The goal is to form a functional map of the cell's processes. As of 2010 a model of genetic interactions is most comprehensive yet to be constructed, containing "the interaction profiles for ~75% of all genes in the Budding yeast".^[18] This model was made from 5.4 million two-gene comparisons in which they preformed a double gene knockout for each combination of the genes studied. The effect of the double knockout on the fitness of the cell was compared to the expected fitness. Expected fitness is determined from the sum of the results on fitness of single gene knockouts for each compared gene. When there is a change in fitness from what is expected the genes are presumed to interact with each other. This was tested by comparing the results to what was previously known. For example, the genes Par32, Ecm30, and Ubp15 had similar interaction profiles to genes involved in the Gap1-sorting module cellular process. Consistent with the results these genes, when knocked out disrupted that process confirming that they are part of it.^[18] From this 170,000 gene interactions were found and genes with similar interaction patterns were groped together. Genes with similar genetic interaction profiles tend to be part of the same pathway or biological process.^[19] This information was used to construct a global network of gene interactions organized by function. This network can be used to predict the function of uncharacterized genes based on the functions of genes they are grouped with.^[18]

Other tools in yeast research [edit]

Approaches that can be applied in many different fields of biological and medicinal science have been developed by yeast scientists. These include yeast two-hybrid for studying protein interactions and tetrad analysis. Other resources, include a gene deletion library including ~4700 viable haploid single gene deletion strains. A GFP fusion strain library used to study protein localisation and a TAP tag library used to purify protein from yeast cell extracts. These can be requested from the stock centers which can be found at the yeast wiki, which is hosted by the Saccharomyces Genome Database.

Astrobiology [edit]

Among other microorganisms, a sample of living S. cerevisiae was included in the Living Interplanetary Flight Experiment, which would have completed a three-year interplanetary round-trip in a small capsule aboard the Russian Fobos-Grunt spacecraft, launched in late 2011.^[20][21] The goal was to test whether selected organisms could survive a few years in deep space by flying them through interplanetary space. The experiment would have tested one aspect of transpermia, the hypothesis that life could survive space travel, if protected inside rocks blasted by impact off one planet to land on another.^[20][21][22] Fobos-Grunt's mission ended unsuccessfully however when it failed to escape low Earth orbit. The spacecraft along with its instruments fell into the Pacific Ocean in an uncontrolled re-entry on January 15, 2012.

Yeast in commercial applications [edit]

Brewing [edit]

Saccharomyces cerevisiae is used in brewing beer, when it is sometimes called a top-fermenting or top-cropping yeast. It is so called because during the fermentation process its hydrophobic surface causes the flocs to adhere to CO₂ and rise to the top of the fermentation vessel. Top-fermenting yeasts are fermented at higher temperatures than the lager yeast Saccharomyces pastorianus, and the resulting beers have a different flavor than the same beverage fermented with a lager yeast. "Fruity esters" may be formed if the yeast undergoes temperatures near 21 °C (70 °F), or if the fermentation temperature of the beverage fluctuates during the process. Lager yeast normally ferments at a temperature of approximately 5 °C (41 °F), where Saccharomyces cerevisiae becomes dormant.

Uses in aquaria [edit]

Owing to the high cost of commercial CO₂ cylinder systems, CO₂ injection by yeast is one of the most popular DIY approaches followed by aquaculturists for providing CO₂ to underwater aquatic plants. The yeast culture is, in general, maintained in plastic bottles, and typical systems provide one bubble every 3–7 seconds. Various approaches have been devised to allow proper absorption of the gas into the water.

Yeast strains [edit]

The following yeast strains have been used in numerous research projects, e.g. for yeast two-hybrid screens. Note that many yeast strains come as pairs of haploid a and alpha strains (indicated by MATa or MATα) which can be mated to form diploid strains. Strains are usually characterized by their genetic differences to the sequenced "standard" strain S288C. For instance, strain AH109 has its gal4 gene deleted (indicated by a Greek Δ) and a mutation in its trp gene. More strains can be found on the SGD Wiki.^[23]

AH109 [edit]

Genotype:^[24] MATa, trp 1–901, leu2-3, 112, ura3-52, his3- 200, Δgal4, Δgal80, LYS2: GAL1UAS-GAL1TATA-HIS3, GAL2UAS- GAL2TATA-ADE2, URA3: MEL1UAS-MEL1TATA-lacZ)

PJ69-4alpha [edit]

Genotype:^[25] MATα trp1-901 leu2-3,112 ura3-52 his3-200 gal4(deleted) gal80(deleted) LYS2::GAL1-HIS3 GAL2-ADE2 met2::GAL7-lacZ

PJ69-4a [edit]

Genotype:^[25] MATa trp1-901 leu2-3,112 ura3-52 his3-200 gal4(deleted) gal80(deleted) LYS2::GAL1-HIS3 GAL2-ADE2 met2::GAL7-lacZ

Y187 [edit]

Y187 has been sold commercially by Clontech^[26] since at least 2000 and is used as a partner with strain AH109 in mating assays.^[27]

Genotype:^[28] MATα, ura3-52, his3-200, ade2-101, trp1-901, leu2-3, 112, gal4Δ, met–, gal80Δ, URA3::GAL1_UAS-GAL1_TATA-lacZ.

See also [edit]

• Saccharomyces cerevisiae extracts Vegemite, Marmite, Cenovis, Guinness Yeast Extract, EpiCor, mannan oligosaccharides, pgg-glucan, zymosan

References [edit]

10. David B. Jansma, REGULATlON AND VARlATlON OF SUBUNITS OF RNA POLYMERASE II IN SACCHAROMYCES CEREVISIAE http://www.collectionscanada.gc.ca/obj/s4/f2/dsk1/tape7/PQDD_0003/NQ41179.pdf

Further reading [edit]

• Arroyo-López FN, Orlić S, Querol A, Barrio E (May 2009). "Effects of temperature, pH and sugar concentration on the growth parameters of Saccharomyces cerevisiae, S. kudriavzevii and their interspecific hybrid". Int. J. Food Microbiol. 131 (2–3): 120–7. doi:10.1016/j.ijfoodmicro.2009.01.035. PMID 19246112. 

Saccharomyces boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. It is related to, but distinct from, Saccharomyces cerevisiae in several taxonomic, metabolic, and genetic properties.^[1] S. boulardii has been shown to maintain and restore^{[citation needed]} the natural flora in the large and small intestine; it is classified as a probiotic. However, in immunocompromised and immunosupressed patients, it can cause disease in the form of a systemic blood infection, fungemia, or localized infection^{[citation needed]}.

Boulard first isolated the yeast after he observed natives of Southeast Asia chewing on the skin of lychee and mangosteen in an attempt to control the symptoms of cholera. S. boulardii has been shown to be non-pathogenic, non-systemic (it remains in the gastrointestinal tract rather than spreading elsewhere in the body), and grows at the unusually high temperature of 37 °C (98.6°F).^[2]

S. boulardii is often marketed as a probiotic in a lyophilized form and is therefore often referred to as Saccharomyces boulardii lyo.

Medical uses

There are numerous randomized, double-blind placebo-controlled studies showing the efficacy of S. boulardii in the treatment and prevention of gastrointestinal disorders.^[3]

Acute diarrhea

Two studies each showed a significant reduction in the symptoms of acute gastroenteritis in children, versus placebo, by measuring frequency of bowel movements and other criteria.^[4][5] Children over three months are recommended to take two doses of 250 mg a day (BID) for five days to treat acute diarrhea. Children under three months are recommended to take half a 250 mg capsule or sachet twice daily for five days.

A prospective placebo-controlled study found a significant reduction in symptoms of diarrhea in adults as well taking 250 mg of S. boulardii twice a day for five days or until symptoms are relieved.^[6]

Recurrent Clostridium difficile infection

Administration of two 500 mg doses per day of S. boulardii when given with one of two antibiotics (vancomycin or metronidazole) was found to significantly reduce the rate of recurrent Clostridium difficile (pseudomembranous colitis) infection. No significant benefit was found for prevention of an initial episode of Clostridium difficile-associated disease.^[7]

Irritable bowel syndrome

A prospective placebo-controlled study found patients with diarrhea predominant irritable bowel syndrome (IBS) had a significant reduction on the number and consistency of bowel movements.^[8]

Inflammatory bowel disease

Further benefits to inflammatory bowel disease (IBD) patients have been suggested in the prevention of relapse in Crohn's disease patients currently in remission^[9] and benefits to ulcerative colitis patients currently presenting with moderate symptoms.^[10] The recommended dosage is three 250 mg capsules a day (TID).^{[citation needed]}

Travelers' diarrhea

Austrian vacationers taking S. boulardii traveling around the world were found to have significantly fewer occurrences of travelers' diarrhea than those taking placebo. The more S. boulardii taken in prevention, starting five days before leaving, the higher the reduction in diarrhea reported. The reduction was also found to be dependent upon where the vacationer traveled.^[11] The recommended dosage is one 250 mg capsule or sachet per day (QD).

Antibiotic-associated diarrhea

There is evidence for its use in the prophylactic (preventative) treatment of antibiotic-associated diarrhea (AAD) in adults.^[12] There is further evidence for its use to prevent AAD in children.^[13]

HIV/AIDS-associated diarrhea

S. boulardii has been shown to significantly increase the recovery rate of stage IV AIDS patients suffering from diarrhea versus placebo. On average, patients receiving S. boulardii gained weight while the placebo group lost weight over the 18 month trial.^[14] There were no reported adverse reaction observed in these immunocompromised patients.

Mechanisms of action

Antitoxin effects

S. boulardii secretes a 54 kDa protease, in vivo. This protease has been shown to both degrade toxins A and B, secreted from Clostridium difficile, and inhibit their binding to receptors along the brush border. This leads to a reduction in the enterotoxinic and cytotoxic effects of C. difficile infection.^[15]

Antimicrobial effects

Escherichia coli and Salmonella typhimurium, two pathogenic bacteria often associated with acute infectious diarrhea, were shown to strongly adhere to mannose on the surface of S. boulardii via lectin receptors (adhesins). Once the invading microbe is bound to S. boulardii, it is prevented from attaching to the brush border; it is then eliminated from the body during the next bowel movement.^[16]

Trophic effects on enterocytes

The hypersecretion of water and electrolytes (including chloride ions), caused by cholera toxin during a Vibrio cholerae infection, can be reduced significantly with the introduction of S. boulardii. A 120 kDa protease secreted by S. boulardii has been observed to have an effect on enterocytes lining the large and small intestinal tract–inhibiting the stimulation of adenylate cyclase, which led to the reduction in enterocytic cyclic adenosine monophosphate (cAMP) production and chloride secretion.^[17]

During an E. coli infection, myosin light chain (MLC) is phosphorylated leading to the degradation of the tight junctions between intestinal mucosa enterocytes. S. boulardii has been shown to prevent this phosphorylation, leading to a reduction in mucosal permeability and thus a decrease in the translocation of the pathogenic bacteria.^[18]

Polyamines (spermidine and spermine) have been observed to be released from S. boulardii in the rat ileum. Polyamines have been theorized to stimulate the maturation and turnover of small intestine enterocytes. This could aid in the increased recovery rate of a patient from diarrhea.^[19]

Anti-inflammatory effects

Interleukin 8 (IL-8) is a proinflammatory cytokine secreted during an E. coli infection in the gut. S. boulardii has been shown to decrease the secretion of IL-8 during an E. coli infection; S. boulardii could have a protective effect in inflammatory bowel disease.^[18] Saccharomyces boulardii may exhibit part of its anti-inflammatory potential through modulation of dendritic cell phenotype, function and migration by inhibition of their immune response to bacterial microbial surrogate antigens such as lipopolysaccharide (LPS). A recent study showed that culture of primary human myeloid dendritic cells CD1c+CD11c+CD123- DC (mDC) in the presence of Saccharomyces boulardii culture supernatant (active component molecular weight < 3kDa as evaluated by membrane partition chromatography) significantly reduced expression of the co-stimulatory molecules CD40 and CD80 and the dendritic cell mobilization marker CC-chemokine receptor CCR7 (CD197) induced by the prototypical microbial antigen lipopolysaccharide (LPS). Moreover, secretion key pro-inflammatory cytokines like TNF-α and IL-6 were notably reduced, while the secretion of anti-inflammatory IL-10 did increase. Finally Saccharomyces boulardii supernatant inhibited the proliferation of naïve T-cells in a mixed lymphocyte reaction (MLR) with mDC.^[20]

Increased levels of disaccharidases

The trophic effect on enterocytes has been shown to increase levels of disaccharidases such as lactase, sucrase, maltase, glucoamylase, and N-aminopeptidase in the intestinal mucosa of humans and rats. This can lead to the increased breakdown of disaccharides into monosaccharides that can then be absorbed into the bloodstream via enterocytes.^[21][22] This can help in the treatment of diarrhoea, as the level of enzymatic activity has diminished and carbohydrate cannot be degraded and absorbed.

Increased immune response

S. boulardii induces the secretion of Immunoglobulin A (IgA) in the small intestine of the rat.^[23]

Human disease

Saccharomyces fungemia can occur in immunocomprised patients, especially those with certain digestive disorders, or patients with a central venous catheter. Administration of an antimycotic (antifungal) usually leads to patient recovery from this systemic infection. Patients with yeast allergies are not encouraged to take S. boulardii. In particular, highly concentrated form, marketed as probiotic supplements for the treatment of Clostridium difficile colitis, can possibly cause fungemia in critically ill patients.^[24]

References