High lipid accumulation in Yarrowia lipolytica cultivated under double limitation of nitrogen and magnesium

Bellou, Stamatia; Triantaphyllidou, Irene-Eva; Mizerakis, Panagiotis; Aggelis, George

doi:10.1016/j.jbiotec.2016.08.001

Cited by 126 publications

(80 citation statements)

References 53 publications

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“…For example, proteomic analysis demonstrated that nitrogen depletion can upregulate the glycolytic pathway, while the activity of TCA cycle was retarded, thus, leading more carbon flux to fatty acid biosynthesis in Mucor circinelloides (Tang et al, 2016). Other types of nutrient starvation that can enhance lipid accumulation include phosphate, silicon, and sulfate limitation (Wu et al, 2011; Ren et al, 2013; Bellou et al, 2016b; Ota et al, 2016). …”

Section: Lipid Accumulation In Oleaginous Microorganisms Under Differmentioning

confidence: 99%

Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

et al. 2017

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Microbial oils, which are mainly extracted from yeasts, molds, and algae, have been of considerable interest as food additives and biofuel resources due to their high lipid content. While these oleaginous microorganisms generally produce only small amounts of lipids under optimal growth conditions, their lipid accumulation machinery can be induced by environmental stresses, such as nutrient limitation and an inhospitable physical environmental. As common second messengers of many stress factors, reactive oxygen species (ROS) may act as a regulator of cellular responses to extracellular environmental signaling. Furthermore, increasing evidence indicates that ROS may act as a mediator of lipid accumulation, which is associated with dramatic changes in the transcriptome, proteome, and metabolome. However, the specific mechanisms of ROS involvement in the crosstalk between extracellular stress signaling and intracellular lipid synthesis require further investigation. Here, we summarize current knowledge on stress-induced lipid biosynthesis and the putative role of ROS in the control of lipid accumulation in oleaginous microorganisms. Understanding such links may provide guidance for the development of stress-based strategies to enhance microbial lipid production.

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Section: Lipid Accumulation In Oleaginous Microorganisms Under Differmentioning

confidence: 99%

Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

et al. 2017

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“…Citrate is a key intermediate in both catabolism and anabolism, and it occupies a prominent position in the yeast energy metabolism, and therefore, its production is affected by the cultivation conditions and the energy and C-source used. Despite an increased number of biotechnological applications performed by several wild or genetically engineered Y. lipolytica strains [13–15, 20–22] relatively few studies have focused on the metabolism, growth kinetics and product formation in mixed substrate fermentation [7, 23]. In general, dual substrate fermentation by oleaginous yeasts has been little investigated [24, 25].…”

Section: Introductionmentioning

confidence: 99%

Substrates and oxygen dependent citric acid production by Yarrowia lipolytica: insights through transcriptome and fluxome analyses

et al. 2017

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BackgroundUnlike the well-studied backer yeast where catabolite repression represents a burden for mixed substrate fermentation, Yarrowia lipolytica, an oleaginous yeast, is recognized for its potential to produce single cell oils and citric acid from different feedstocks. These versatilities of Y. lipolytica with regards to substrate utilization make it an attractive host for biorefinery application. However, to develop a commercial process for the production of citric acid by Y. lipolytica, it is necessary to better understand the primary metabolism and its regulation, especially for growth on mixed substrate.ResultsControlling the dissolved oxygen concentration (pO2) in Y. lipolytica cultures enhanced citric acid production significantly in cultures grown on glucose in mono- or dual substrate fermentations, whereas with glycerol as mono-substrate no significant effect of pO2 was found on citrate production. Growth on mixed substrate with glucose and glycerol revealed a relative preference of glycerol utilization by Y. lipolytica. Under optimized conditions with pO2 control, the citric acid titer on glucose in mono- or in dual substrate cultures was 55 and 50 g/L (with productivity of 0.6 g/L*h in both cultures), respectively, compared to a maximum of 18 g/L (0.2 g/L*h) with glycerol in monosubstrate culture. Additionally, in dual substrate fermentation, glycerol limitation was found to trigger citrate consumption despite the presence of enough glucose in pO2-limited culture. The metabolic behavior of this yeast on different substrates was investigated at transcriptomic and 13C-based fluxomics levels.ConclusionUpregulation of most of the genes of the pentose phosphate pathway was found in cultures with highest citrate production with glucose in mono- or in dual substrate fermentation with pO2 control. The activation of the glyoxylate cycle in the oxygen limited cultures and the imbalance caused by glycerol limitation might be the reason for the re-consumption of citrate in dual substrate fermentations. This study provides interesting targets for metabolic engineering of this industrial yeast.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-017-0690-0) contains supplementary material, which is available to authorized users.

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“…Technological and cellular-level improvements are required to reduce processing costs and achieve higher productivity with wider range of low-value substrates [4]. Prior to genetic modification, the lipid content of a wild-type Y. lipolytica strain rarely reaches 20% DCW [5].…”

Section: Introductionmentioning

confidence: 99%

Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

Abghari

Chen

2017

Fermentation

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Increasing demand for plant oil for food, feed, and fuel production has led to food-fuel competition, higher plant lipid cost, and more need for agricultural land. On the other hand, the growing global production of biodiesel has increased the production of glycerol as a by-product. Efficient utilization of this by-product can reduce biodiesel production costs. We engineered Yarrowia lipolytica (Y. lipolytica) at various metabolic levels of lipid biosynthesis, degradation, and regulation for enhanced lipid and citric acid production. We used a one-step double gene knock-in and site-specific gene knock-out strategy. The resulting final strain combines the overexpression of homologous DGA1 and DGA2 in a POX-deleted background, and deletion of the SNF1 lipid regulator. This increased lipid and citric acid production in the strain under nitrogen-limiting conditions (C/N molar ratio of 60). The engineered strain constitutively accumulated lipid at a titer of more than 4.8 g/L with a lipid content of 53% of dry cell weight (DCW). The secreted citric acid reached a yield of 0.75 g/g (up to~45 g/L) from pure glycerol in 3 days of batch fermentation using a 1-L bioreactor. This yeast cell factory was capable of simultaneous lipid accumulation and citric acid secretion. It can be used in fed-batch or continuous bioprocessing for citric acid recovery from the supernatant, along with lipid extraction from the harvested biomass.

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High lipid accumulation in Yarrowia lipolytica cultivated under double limitation of nitrogen and magnesium

Cited by 126 publications

References 53 publications

Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

Reactive Oxygen Species-Mediated Cellular Stress Response and Lipid Accumulation in Oleaginous Microorganisms: The State of the Art and Future Perspectives

Substrates and oxygen dependent citric acid production by Yarrowia lipolytica: insights through transcriptome and fluxome analyses

Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

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