Lipid biosynthesis in yeasts: A comparison of the lipid biosynthetic pathway between the model nonoleaginous yeast <i>Saccharomyces cerevisiae</i> and the model oleaginous yeast <i>Yarrowia lipolytica</i>

Fakas, Stylianos

doi:10.1002/elsc.201600040

Cited by 83 publications

(115 citation statements)

References 97 publications

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“…Biosynthesis of TAG requires G3P backbone that is acylated by fatty acids [45]. The de novo synthesis of fatty acids uses starting units of acetyl-CoA and malonyl-CoA, as well as the cofactor and energy in the form of NADPH and ATP [46]. In Y. lipolytica, acetyl-CoA carboxylase (ACC1) catalyzes the first committed step of fatty acid synthesis.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

Abghari

Chen

2017

Fermentation

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“…The yeast Yarrowia lipolytica has been considered as a model for the study of the lipid biosynthetic pathway (Figure ) and its regulation in oleaginous microorganisms (see Fakas, () for a recent review). Y .…”

Section: Introductionmentioning

confidence: 99%

“…lipolytica should be done with care though, because some of the key steps and enzymes (e.g. ATP:citrate lyase) that are involved in lipid biosynthesis differ between these two microorganisms (Fakas, ). It would then seem advantageous to study the key regulatory steps in Y .…”

Section: Introductionmentioning

confidence: 99%

“…The yeast Yarrowia lipolytica has been considered as a model for the study of the lipid biosynthetic pathway ( Figure 1) and its regulation in oleaginous microorganisms (see Fakas, (2016) for a recent review). Y. lipolytica presents several advantages as a model organism because its genetics is known and tools for its genetic manipulation are becoming increasingly available (Nicaud, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of phosphatidic acid phosphatase activity in the oleaginous yeastYarrowia lipolyticaand its role in lipid biosynthesis

Hardman

McFalls

Fakas

2016

Yeast

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Phosphatidic acid phosphatase (PAP) catalyses the committed step of triacylglycerol (TAG) biosynthesis and thus regulates the amounts of TAG produced by the cell. TAG is the target of biotechnological processes developed for the production of food lipids or biofuels. These processes are using oleaginous microorganisms like the yeast Yarrowia lipolytica as the TAG producers. Thus manipulating key enzymatic activities like PAP in Y. lipolytica could drive lipid biosynthesis towards TAG production and increase TAG yields. In this study, PAP activity in Y. lipolytica was characterized in detail and its role in lipid biosynthesis was addressed. PAP activity increased 2.5-fold with the addition of Mg (1 mm) in the assay mixture, which means that most of the PAP activity was due to Mg -dependent PAP enzymes (e.g. Pah1, App1). In contrast, N-ethylmaleimide (NEM) potently inhibited PAP activity, indicating the presence of NEM-sensitive PAP enzymes (e.g. App1, Lpp1). Localization studies revealed that the majority of PAP activity resides in the membrane fraction, while the cytosolic fraction harbours only a small amount of activity. PAP activity was regulated in a growth-dependent manner, being induced at the early exponential phase and declining thereafter. PAP activity did not correlate with TAG synthesis, which increased as cells progressed from the exponential phase to the early stationary phase. In stationary phase, TAG was mobilized with the concomitant synthesis of sterols and sterol esters. These results provide the first insights into the role of PAP in lipid biosynthesis by Y. lipolytica. Copyright © 2016 John Wiley & Sons, Ltd.

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“…[7] Common oleaginous microorganisms include yeasts, algae, moulds, and bacteria. [9] To date, typical yeasts indentified include Rhodosporidium toruloides, Rhodotorula glutinis, Lipomyces starkeyi, Y. lipolytica, Cryptococcus albidus, Cryptococcus curvatus, and Trichosporon pullulans. [9] To date, typical yeasts indentified include Rhodosporidium toruloides, Rhodotorula glutinis, Lipomyces starkeyi, Y. lipolytica, Cryptococcus albidus, Cryptococcus curvatus, and Trichosporon pullulans.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction

Zeng

Liu

Shi

et al. 2018

Euro J Lipid Sci & Tech

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The non‐conventional yeast Yarrowia lipolytica have been receiving growing attention due to its excellent lipid accumulation capacity. Microbial lipid have attracted widespread interest due to their broad applications as dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. With the development of whole‐genome sequencing, many effective genetic tools, including transformation systems, promoter systems, genomic integration and genome editing tools, have been applied in Y. lipolytica to enhance the overproduction of lipid. It can be genetically engineered for high lipid production via the upregulation of synthetic precursor and lipid synthesis pathways, the downregulation or disruption of competing pathways such as β‐oxidation, and elimination of inhibitory factors. In this review, the lipid metabolism, available genetic tools, and recent advances in metabolic engineering of Y. lipolytica for the overproduction of lipid and lipid‐derived chemicals is summarized. Future prospects of lipid biosynthesis in Y. lipolytica are discussed in light of the current progress, challenges, and trends in this field. Guidelines for future studies are also proposed. Practical Applications: General concerns about climate change, oil price crisis, and the increasing study for renewable energy are driving bio‐lipid as promising alternatives to fossil fuel. Over the past few decades, microbial lipid have been widely applied in dietary supplements, cosmetic additives, oleochemicals, and renewable starting materials for the production of fossil fuel. The non‐conventional yeast Yarrowia lipolytica have become an attractive metabolic engineering host for the production of microbial lipids due to its ability to synthesize them in large quantities. This review illuminates the lipid biosynthesis and degradation of Y. lipolytica, and summarizes the metabolic engineering efforts which have targeted a variety of biosynthetic biosynthetic pathway to efficiently convert carbon source to lipid in oleaginous Y. lipolytica. Schematic diagram of lipid and triacylglyceride biosynthesis, including the native and heterologous biosynthesis pathways of fatty acids in Y. lipolytica.

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Lipid biosynthesis in yeasts: A comparison of the lipid biosynthetic pathway between the model nonoleaginous yeast Saccharomyces cerevisiae and the model oleaginous yeast Yarrowia lipolytica

Cited by 83 publications

References 97 publications

Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

Characterization of phosphatidic acid phosphatase activity in the oleaginous yeastYarrowia lipolyticaand its role in lipid biosynthesis

Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction

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