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Molecules (Basel, Switzerland) Apr 2022Yarrowia lipolytica, an oleagineous species of yeast, is a carrier of various important nutrients. The biomass of this yeast is an extensive source of protein, exogenous... (Review)
Review
Yarrowia lipolytica, an oleagineous species of yeast, is a carrier of various important nutrients. The biomass of this yeast is an extensive source of protein, exogenous amino acids, bioavailable essenctial trace minerals, and lipid compounds as mainly unsaturated fatty acids. The biomass also contains B vitamins, including vitamin B12, and many other bioactive components. Therefore, Y. lipolytica biomass can be used in food supplements for humans as safe and nutritional additives for maintaining the homeostasis of the organism, including for vegans and vegetarians, athletes, people after recovery, and people at risk of B vitamin deficiencies.
Topics: Biomass; Humans; Yarrowia
PubMed: 35408699
DOI: 10.3390/molecules27072300 -
FEBS Letters May 2022Ergothioneine is a naturally occurring antioxidant that has shown potential in ameliorating neurodegenerative and cardiovascular diseases. In this study, we investigated...
Ergothioneine is a naturally occurring antioxidant that has shown potential in ameliorating neurodegenerative and cardiovascular diseases. In this study, we investigated the potential of the Crabtree-negative, oleaginous yeast Yarrowia lipolytica as an alternative host for ergothioneine production. We expressed the biosynthetic enzymes EGT1 from Neurospora crassa and EGT2 from Claviceps purpurea to obtain 158 mg·L of ergothioneine in small-scale cultivation, with an additional copy of each gene improving the titer to 205 mg·L . The effect of phosphate limitation on ergothioneine production was studied, and finally, a phosphate-limited fed-batch fermentation in 1 L bioreactors yielded 1.63 ± 0.04 g·L ergothioneine in 220 h, corresponding to an overall volumetric productivity of 7.41 mg·L ·h , showing that Y. lipolytica is a promising host for ergothioneine production.
Topics: Bioreactors; Ergothioneine; Fermentation; Metabolic Engineering; Phosphates; Yarrowia
PubMed: 34817066
DOI: 10.1002/1873-3468.14239 -
TheScientificWorldJournal 2014Yarrowia lipolytica is a nonpathogenic dimorphic aerobic yeast that stands out due to its ability to grow in hydrophobic environments. This property allowed this yeast... (Review)
Review
Yarrowia lipolytica is a nonpathogenic dimorphic aerobic yeast that stands out due to its ability to grow in hydrophobic environments. This property allowed this yeast to develop an ability to metabolize triglycerides and fatty acids as carbon sources. This feature enables using this species in the bioremediation of environments contaminated with oil spill. In addition, Y. lipolytica has been calling the interest of researchers due to its huge biotechnological potential, associated with the production of several types of metabolites, such as bio-surfactants, γ-decalactone, citric acid, and intracellular lipids and lipase. The production of a metabolite rather than another is influenced by the growing conditions to which Y. lipolytica is subjected. The choice of carbon and nitrogen sources to be used, as well as their concentrations in the growth medium, and the careful determination of fermentation parameters, pH, temperature, and agitation (oxygenation), are essential for efficient metabolites production. This review discusses the biotechnological potential of Y. lipolytica and the best growing conditions for production of some metabolites of biotechnological interest.
Topics: Biotechnology; Yarrowia
PubMed: 24715814
DOI: 10.1155/2014/476207 -
Microbial Cell Factories Nov 2019Yarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the... (Review)
Review
Yarrowia lipolytica has emerged as a biomanufacturing platform for a variety of industrial applications. It has been demonstrated to be a robust cell factory for the production of renewable chemicals and enzymes for fuel, feed, oleochemical, nutraceutical and pharmaceutical applications. Metabolic engineering of this non-conventional yeast started through conventional molecular genetic engineering tools; however, recent advances in gene/genome editing systems, such as CRISPR-Cas9, transposons, and TALENs, has greatly expanded the applications of synthetic biology, metabolic engineering and functional genomics of Y. lipolytica. In this review we summarize the work to develop these tools and their demonstrated uses in engineering Y. lipolytica, discuss important subtleties and challenges to using these tools, and give our perspective on important gaps in gene/genome editing tools in Y. lipolytica.
Topics: Gene Editing; Gene Expression Regulation; Genetic Engineering; Metabolic Engineering; Yarrowia
PubMed: 31783869
DOI: 10.1186/s12934-019-1259-x -
Journal of Industrial Microbiology &... Feb 2023β-Carotene is a kind of high-value tetraterpene compound, which shows various applications in medical, agricultural, and industrial areas owing to its antioxidant,...
UNLABELLED
β-Carotene is a kind of high-value tetraterpene compound, which shows various applications in medical, agricultural, and industrial areas owing to its antioxidant, antitumor, and anti-inflammatory activities. In this study, Yarrowia lipolytica was successfully metabolically modified through the construction and optimization of β-carotene biosynthetic pathway for β-carotene production. The β-carotene titer in the engineered strain Yli-C with the introduction of the carotenogenesis genes crtI, crtE, and crtYB can reach 34.5 mg/L. With the overexpression of key gene in the mevalonate pathway and the enhanced expression of the fatty acid synthesis pathway, the β-carotene titer of the engineered strain Yli-CAH reached 87 mg/L, which was 152% higher than that of the strain Yli-C. Through the further expression of the rate-limiting enzyme tHMGR and the copy number of β-carotene synthesis related genes, the β-carotene production of Yli-C2AH2 strain reached 117.5 mg/L. The final strain Yli-C2AH2 produced 2.7 g/L β-carotene titer by fed-batch fermentation in a 5.0-L fermenter. This research will greatly speed up the process of developing microbial cell factories for the commercial production of β-carotene.
ONE-SENTENCE SUMMARY
In this study, the β-carotene synthesis pathway in engineered Yarrowia lipolytica was enhanced, and the fermentation conditions were optimized for high β-carotene production.
Topics: Fermentation; Yarrowia; beta Carotene; Metabolic Engineering; Bioreactors
PubMed: 37055369
DOI: 10.1093/jimb/kuad009 -
Trends in Biotechnology Feb 2023Yarrowia lipolytica possesses natural and engineered traits that make it a good host for the industrial bioproduction of chemicals, fuels, foods, and pharmaceuticals. In... (Review)
Review
Yarrowia lipolytica possesses natural and engineered traits that make it a good host for the industrial bioproduction of chemicals, fuels, foods, and pharmaceuticals. In recent years, academic and industrial researchers have assessed its potential, developed synthetic biology techniques, improved its features, scaled its processes, and identified its limitations. Both publications and patents related to Y. lipolytica have shown a drastic increase during the past decade. Here, we discuss the characteristics of this yeast that make it suitable for industry and the remaining challenges for its wider use at large scale. We present evidence herein that shows the importance and potential of Y. lipolytica in bioproduction such that it may soon be one of the preferred choices of industry.
Topics: Yarrowia; Metabolic Engineering; Industry; Synthetic Biology
PubMed: 35940976
DOI: 10.1016/j.tibtech.2022.07.006 -
Microorganisms Apr 2020Sugar alcohols and organic acids that derive from the metabolism of certain microorganisms have a panoply of applications in agro-food, chemical and pharmaceutical... (Review)
Review
Sugar alcohols and organic acids that derive from the metabolism of certain microorganisms have a panoply of applications in agro-food, chemical and pharmaceutical industries. The main challenge in their production is to reach a productivity threshold that allow the process to be profitable. This relies on the construction of efficient cell factories by metabolic engineering and on the development of low-cost production processes by using industrial wastes or cheap and widely available raw materials as feedstock. The non-conventional yeast has emerged recently as a potential producer of such metabolites owing its low nutritive requirements, its ability to grow at high cell densities in a bioreactor and ease of genome edition. This review will focus on current knowledge on the synthesis of the most important sugar alcohols and organic acids in .
PubMed: 32326622
DOI: 10.3390/microorganisms8040574 -
Biotechnology Advances Dec 2018The non-conventional oleaginous yeast Yarrowia lipolytica shows great industrial promise. It naturally produces certain compounds of interest but can also artificially... (Review)
Review
The non-conventional oleaginous yeast Yarrowia lipolytica shows great industrial promise. It naturally produces certain compounds of interest but can also artificially generate non-native metabolites, thanks to an engineering process made possible by the significant expansion of a dedicated genetic toolbox. In this review, we present recently developed synthetic biology tools that facilitate the manipulation of Y. lipolytica, including 1) DNA assembly techniques, 2) DNA parts for constructing expression cassettes, 3) genome-editing techniques, and 4) computational tools.
Topics: CRISPR-Cas Systems; Gene Editing; Metabolic Engineering; Synthetic Biology; Yarrowia
PubMed: 30315870
DOI: 10.1016/j.biotechadv.2018.10.004 -
Applied Microbiology and Biotechnology Nov 2018The oleaginous yeast Yarrowia lipolytica is widely used for the production of both bulk and fine chemicals, including organic acids, fatty acid-derived biofuels and... (Review)
Review
The oleaginous yeast Yarrowia lipolytica is widely used for the production of both bulk and fine chemicals, including organic acids, fatty acid-derived biofuels and chemicals, polyunsaturated fatty acids, single-cell proteins, terpenoids, and other valuable products. Consequently, it is becoming increasingly popular for metabolic engineering applications. Multiple gene manipulation tools including URA blast, Cre/LoxP, and transcription activator-like effector nucleases (TALENs) have been developed for metabolic engineering in Y. lipolytica. However, the low efficiency and time-consuming procedures involved in these methods hamper further research. The emergence of the CRISPR/Cas system offers a potential solution for these problems due to its high efficiency, ease of operation, and time savings, which can significantly accelerate the genomic engineering of Y. lipolytica. In this review, we summarize the research progress on the development of CRISPR/Cas systems for Y. lipolytica, including Cas9 proteins and sgRNA expression strategies, as well as gene knock-out/knock-in and repression/activation applications. Finally, the most promising and tantalizing future prospects in this area are highlighted.
Topics: Bacterial Proteins; CRISPR-Cas Systems; Clustered Regularly Interspaced Short Palindromic Repeats; Metabolic Engineering; Yarrowia
PubMed: 30238143
DOI: 10.1007/s00253-018-9366-x -
Microbial Cell Factories Jul 2022Eukaryotic cells are often preferred for the production of complex enzymes and biopharmaceuticals due to their ability to form post-translational modifications and...
BACKGROUND
Eukaryotic cells are often preferred for the production of complex enzymes and biopharmaceuticals due to their ability to form post-translational modifications and inherent quality control system within the endoplasmic reticulum (ER). A non-conventional yeast species, Yarrowia lipolytica, has attracted attention due to its high protein secretion capacity and advanced secretory pathway. Common means of improving protein secretion in Y. lipolytica include codon optimization, increased gene copy number, inducible expression, and secretory tag engineering. In this study, we develop effective strategies to enhance protein secretion using the model heterologous enzyme T4 lysozyme.
RESULTS
By engineering the commonly used native lip2prepro secretion signal, we have successfully improved secreted T4 lysozyme titer by 17-fold. Similar improvements were measured for other heterologous proteins, including hrGFP and [Formula: see text]-amylase. In addition to secretion tag engineering, we engineered the secretory pathway by expanding the ER and co-expressing heterologous enzymes in the secretion tag processing pathway, resulting in combined 50-fold improvement in T4 lysozyme secretion.
CONCLUSIONS
Overall, our combined strategies not only proved effective in improving the protein production in Yarrowia lipolytica, but also hint the possible existence of a different mechanism of secretion regulation in ER and Golgi body in this non-conventional yeast.
Topics: Endoplasmic Reticulum; Muramidase; Protein Transport; Secretory Pathway; Yarrowia
PubMed: 35786380
DOI: 10.1186/s12934-022-01863-9