Saccharomyces: Is a Necessary Organism or a Biological Warrior?

Abstract

Saccharomyces is a eukaryotic organism that possesses approximately 6,000 known genes since 1996. It has long been used for food, bakeries, drinks, and therapeutics due to its many ingredients and its role in several mechanisms. Saccharomyces can be used as an experimental organism for medicinal products in the pharmaceutical industry. Particularly in public health, the use of Saccharomyces in the production of vaccines is remarkable. It has been alleviated that this yeast helps clarify the function of individual proteins in pathogenic viruses. To clarify virus life and host interactions, virus replication systems in Saccharomyces were interested in scientists. The new antiviral strategies with yeasts suggest the biological mechanism of a pathogen virus. Due to the variety of diseases and current epidemic conditions, these organisms play an essential role in prevention and treatment. This chapter will try to update Saccharomyces’ scientific discoveries with the most recent and up-to-date literature.

1. Introduction

Besides poor treatment and vaccination programs, a healthy immune system and antioxidant mechanism are the essential defenders considering the current viral diseases. The viral diseases hosted in a body has several impacts on organs and systems. Also, long-term drug use or vaccination programs can cause some acute side effects on the body, such as gut microbiota, immunity, lung tissue, etc. Therefore, probiotics, prebiotics, vitamins, natural antioxidants have been generally recommended over the years. Probiotics named live microorganisms have beneficial effects on systems, and they have been used successfully. Prebiotics are non-digestible foods that stimulate intestinal tissue growth and modulate immunity. Vitamins, minerals, and natural antioxidants have been used to enhance immune activity and health in viral diseases. It can be said that all these supplements are essential for adequate homeostasis.

Today, evaluate the most effective, economical, and safe vaccines is a significant challenge. Thus, some crucial organisms have been interested in vaccine production as well as nutrition. Among the different vaccination process, yeasts have a broad interest in the scientific area (Figure 1). These unicellular and saprotrophic fungi have been used as a biological model. They have also been accepted as critical models for experiments due to their cellular structure, components, and rapid growth. Yeast also can be cultured easily and manipulated genetically. These features showed that yeasts are beneficial to identify the cellular mechanism of virus and vaccine programs safely [1, 2].

Figure 1.

Biomedical applications of yeasts.

The yeast Saccharomyces, the essential eukaryotic organism, have been used as a biological model. Nevertheless, there is a notable gene homology in this yeast with human genes. In this chapter, we try to identify the Saccharomyces yeast as a useful model for biological experiments and observe the importance of viruses, viral diseases, and vaccines.

2. Saccharomyces

Saccharomyces cerevisiae is a model organism extensively used to investigate the biology of eukaryotic cells. It is widely used as a cell factory for producing pharmaceuticals, chemicals, and biofuels [3].

Saccharomyces, which is a genus belonging to the Saccharomyces fungus kingdom, includes many yeast species. The name of Saccharomyces is derived from the Latin words saccharo- (sugar) and - Greek mikes (mushrooms). These yeasts were initially suggested in 1680, and named Saccharomyces in 1837. A successful systemic concept on these higher eukaryotes was designed by Mayr [4]. Yeasts’ cultured forms have been used for thousands of years due to rapid reproduction and essential components. Typical features of Saccharomyces are the usage of nitrate and ability for the fermentation of carbohydrates. Saccharomyces have an excellent capacity for ethanol production, and they are suitable yeasts for large-scale fermentation [5]. These important yeasts can be used for the food industry to produce several foods such as bread, beer, wine, distilled spirits, and industrial alcohols. The most knows are S. cerevisiae, S. boullardii, S. pombe, S. pastorianus, and S. paradoxus, mostly used for food and treatments. Nevertheless, these yeasts have a small nucleus and central vacuole and have glucan and mannoproteins on their cell walls. Saccharomyces include a single linear double-stranded DNA, ribosomal proteins, and non-ribosomal molecules, like other eukaryotes. It was suggested that their genetic structure is beneficial for the model organism, especially S. cerevisiae [6].

S. cerevisiae a single celled organism that is used as a model organism. These yeasts have been studied to understand the concept of cell cycle regulation, DNA repair, and other cellular mechanisms. It was also reviewed that a model to identify the mutations in the cell cycle in cancer and some diseases, especially neurodegenerative diseases [7]. However, a form of S. cerevisiae called S. boulardii had been observed in clinical trials for treatment such as inflammation and diarrhea. Mc Farland and Bernasconi reported that S. boulardii is a wild type of Saccharomyces, a pharmaceutical agent [8]. The action of S. boulardii has been described by releasing trypsin-like protease, which inhibits the toxins in inflammations [9].

Schizosaccharomyces pombe is a fission yeast that was isolated in 1893 by Paul Lindner from East African millet beer. It is a model organism for eukaryotic cell biology and molecular biology as well as S. boulardii and S. cerevisiae. In 1590, Mitchison was firstly studied with this yeast in an experimental organism. Eser et al. reported that it could be used to treat diabetes and other diseases [10]. This fission yeast has been studied for eukaryotic RNA metabolism due to its gene expression.

S. bayanus (S. eubayanus), S. paradoxus, and S. pastorianus have similar genome size with S. cerevisiae. They all have been studied for DNA reassociation studies [11]. S. pastorianus is a lager yeast, an interspecific hybrid between S. cerevisiae and another S. bayanus (S. eubayanus) [12]. It is also a synonym of S. carlsbergensis and closely related to genus S. cerevisiae. Another wild type of yeast, S. paradoxus, can be isolated from nature, especially tree exudates or oils. It is an essential type of yeast for genetic and genomic studies. A yeast named S. bayanus (S. eubayanus), which was isolated from the tree, is related to S. cerevisiae and S. pastorianus [13]. S. bayanus has been used for genomic studies, expression patterns, and nucleosomes profiles [14, 15, 16].

Saccharomyces yeasts focus on the dietary field as a probiotic and the process of treating the disease. Belong the probiotic action; these yeasts have several vital roles on mechanisms such as bacterial adhesion, enhancement of immune cells and responses, modulation of the signaling pathways of the host, and improvement of the strengthening of enterocytes [17]. Nevertheless, Saccharomyces are used as model organisms in biological studies, particularly chemicals and pharmaceuticals.

3. Experimental organism for pharmaceutical industry

Over the last fifty years, remarkable progress in our ability to produce advanced drugs has improved people’s health and longevity. Pharmaceutical proteins are one of the fastest-growing groups of medicines and are currently critical to treating many diseases [18].

Proteins have a catalyzer role in several metabolic reactions as well as an essential responsibility for cellular mechanisms. There are unique systems that can be used to produce proteins for the pharmaceutical industry from a single cell to multiple organisms, including eukaryotes, especially yeasts. Dozens of pharmaceutical proteins, including insulin, vaccines, and blood factors, produced by S. cerevisiae, have been commercialized. It was reviewed that yeasts are essential for biological activities, mainly producing the purified product due to its cost-effective, fast production like bacteria and high density of cell cultures [19]. In recent years, indeed, as a model organism, yeasts have been provided to identify the pathogenesis and role for diseases, especially S. cerevisiae and S. pombe.

The yeast Saccharomyces has been accepted as the significant organism for several metabolisms such as cell cycle, biogenesis, protein folding, genetic manipulation, recombination, etc. [20]. S. cerevisiae is a unicellular microbial organism that grows fast, tolerances to chemicals, and cultured easily. It was reported that this yeast could discover the process of diseases because of the conservation of molecular interactions from yeast to humans [21, 22]. On the other hand, S. cerevisiae can be an essential organism for recombinant protein production for pharmacy. It has full cellular organelles and membrane compartments that produce many eukaryotic proteins, including humans’ [23]. Initially, the essential biopharmaceuticals insulin and its analogs have been produced by S. cerevisiae. Researchers have reported other important biopharmaceuticals such as the human serum albumin, hepatitis vaccines, and virus-like particles for vaccination (Table 1). Also, several medicines have been produced with S. cerevisiae until 2012 reported by the European Medicines Agency [18]. Furthermore, current studies showed that metabolic engineering pathways and optimization procedures of S. cerevisiae are essential for producing recombinant proteins for pharmaceuticals and biomedical areas [18, 19]. S. cerevisiae carries out human-like glycoprotein that is efficient for producing recombinant proteins. Protein secretion of S. cerevisiae is complex processing that follows as transcription, translation, translocation, post-translational modifications, folding, peptide cleavage, glycosylation, sorting, and secretion. This important organism enables genetic modifications. It was reported that the first eukaryotic organism sequenced DNA in S. cerevisiae [41]. Due to the protein misfolding and aggregation, S. cerevisiae has been used as a model organism.

Bioparhamaceutical products	Category	References
Human serum albumin	Blood factors	Payne et al. [24]
Recombinant proteins	Protein	Huang et al. [18], Ferrer-Millares et al. [19], Ma et al. [25], Cino [26]
Insulin	Hormone	Martinez et al. [27]
Glucagon	Hormone	Egel-Mitani et al. [28]
Human parathyroid hormone	Hormone	Song et al. [29]
Purified protein for vaccines	Protein	Hadiji-Abbes et al. [30], Zhang et al. [31], King et al. [32], Kaslow and Shiloach [33], Fazlalipour et al. [34].
Virus like particles	Protein	Jacobs et al. [35], Kim et al. [36], Kim et al. [37].
Gene expression systems	Gene	Malak et al. [38], van Ooyen et al. [39], Vierira Gomes et al. [40].

Table 1.

Examples of bioparhamaceutical products of Saccharomyces.

Nevertheless, S. pombe has been accepted as a model organism together with S. cerevisiae. This fission yeast is used as a successful host. It was reviewed that S. pombe and generated strains have significant facilitation for producing drug glucuronides [42, 43]. The classical yeast genetics approaches can be described for S. pombe. It has been accepted as the most ancient yeast molecule. However, S. pombe has been more advanced evolutionarily than other yeasts. S. pombe has become a model organism until 2002 [44, 45].

Recombinant proteins are recognized as an important part of the drug industry. Among these proteins, Saccharomyces has greater attention than others due to their eukaryotic properties, easy genetic manipulation, and capable of modifications. S. cerevisiae emerges as the most common host to express heterologous genes and therapeutic proteins [46]. This organism may provide a simple background for isotype expressions, and thereby drug metabolism studies can be easily associated with genome screens, underlying toxicity, and encoded genomes.

4. Antiviral strategies

While the vaccines currently available have proven invaluable in the fight against infectious diseases and eradicating viruses, there are many drawbacks to the current vaccine preparation or application regimen despite these successes. Certain limitations of conventional vaccines require multiple adjuvants and injections to induce a necessary or optimal immune response. Another reason is the constant increase in the number of post-vaccination allergic reactions or hypersensitivities in a specific group of people [47, 48].

Today, there are several critical viral diseases such as human hepatitis B and C, immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus (SARS), coronavirus-disease 2019 (COVID19), etc. Due to the inadequacy of treatment options for these infections, new antiviral strategies and model organisms, particularly yeast, were of interest to the researchers.

Yeasts have a delivery system for nucleic acids, and thus they can be an alternative for virus description. Besides, a humanized yeast system was identified for yeast/virus systems to study diseases [49]. Yeasts are used for subunit vaccine formulations with producing antigens against viruses. It was reviewed that yeast can be used for vaccine development in such strategies; whole recombinant yeast, virus-like particles, yeast display, and purified protein immunogens [50]. Among yeasts, S. cerevisiae has been accepted as a versatile model organism for viruses’ research, from the wire of public health to vaccine production.

Rosenfeld and Racaniello [51] reported that hepatitis C virus (HCV) was demonstrated in S. cerevisiae, and all proteins for the virus were encoded. Another study reported that S. cerevisiae could safely express the hepatitis B surface antigen in prophylactic vaccines [52]. Researchers observed that yeast could help clarify the function of viruses’ proteins with dissection of RNA viruses’ life cycle [53, 54]. Nevertheless, several protein immunogens can be purified from Saccharomyces. These immunogen proteins derived from yeasts are associated with virus-like particles. Virus-like particles can provide an alternative for viruses, and FDA approved this vaccine for hepatitis B and papillomavirus [55]. Also, the circumsporozoite protein derived from S. cerevisae is an immunodominant antibody of malaria. This preparation increased the antibodies and thereby neutralized the sporozoites [56]. Due to the yeast membrane permeability, S. cerevisiae enables entry to the chemical compounds and provides virus-host interactions. Some researchers showed that beta-glucan of the yeast cell wall could provide the immune response that important for vaccine development [57].

All things considered, the yeast-based carrier system can be a potential model to develop the vaccine insights of virus-host interactions. The yeast strategies can improve the recognition of pathogen antigens peptides, activate the immune response, and also modulate the yeast-based vaccines. Researchers for further pioneering findings have still endured the studies.

5. Future perspectives

There have been many illnesses that have not been controlled by vaccination and new ones as well. Mutation, genetic exchange, environmental and interspecific transference, or human contact are the most emerging diseases. However, new scientific technologies, model organisms and a number of researchers have proven beneficial to vaccination strategies. In this respect, it is possible to observe yeasts for the upcoming vaccines for several diseases.

Yeast engineered to the virus has been accepted as an ideal therapeutic approach. This vaccine’s strategy is improving humoral immunity due to the ability of yeast to the generation of immune responses.

There is a numerous increasing study to obtain the vaccine strategy of yeasts. Studies in yeast proteins and cell wall components, including beta-glucan, may become more critical for vaccine strategies under different phases of clinical trials on animals or humans. According to the essential features of yeast, the yeast-based vaccine strategy is being necessary for vaccine development. It has foreseen that diversity of yeast strains will improve in the future.

6. Conclusion

The yeast system provides invaluable antiviral strategies. Significant studies have been conducted on yeast progression in the identification of viral diseases and antiviral strategies. Based on a better understanding of yeast protein and viruses, the search for new vaccines and medications for viral or pandemic diseases is safer and more effective. However, experiments with animal models and human cells are still underway in many types of yeast. Knowledge of these new biological systems and technologies, models, and organisms will open up new science avenues.

Conflict of interest

The authors declare no conflict of interest.

Acronyms and abbreviations

Appendices and nomenclature

Yeast	The most important eukaryote; Saccharomyces.
Single celled organism	Saccharomyces cerevisiae
Nucleosomes	DNA, RNA
Biopharmaceuticals	insulin and its analogs
Eukaryotes	The organisms whose cells have a nucleus enclosed within a nuclear envelope