Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

Abghari, Ali; Madzak, Catherine; Chen, Shulin

doi:10.3390/fermentation3030040

Cited by 20 publications

(11 citation statements)

References 125 publications

(118 reference statements)

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“…The current price of biodiesel-derived glycerol varied from US $0.06 to US $0.11 per pound [15]. On the basis of microorganisms grown on biodiesel-derived waste glycerol, researchers developed the method of production of 1,3-propanediol [16], biomass-enriched lipids [17][18][19][20][21], carbonic acids (in particular, pyruvic acid [22]), α-ketoglutaric acid [23,24], citric acid [16,25,26], and butanol [27]. However, few reports showed the satisfactory growth of fungi of the genera Mucor, Cunninghamella, Thamnidium, Zygorhynchus, and Mortierella, and similarly for lipid synthesis when cultivated on glycerol [15][16][17][18][19]21,[28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

The Effect of pH and Temperature on Arachidonic Acid Production by Glycerol-Grown Mortierella alpina NRRL-A-10995

et al. 2018

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Arachidonic acid (AA) has a wide range of applications in medicine, pharmacology, diet, infant nutrition, and agriculture, due to its unique biological properties. The microbiological processes involved in AA production usually require carbohydrate substrates. In this paper, we propose a method for AA production from glycerol, an inexpensive and renewable carbon substrate that is produced by the fungal strain, Mortierella alpina NRRL-A-10995. Our experimental results showed that the optimum pH values required for fungal growth and the production of lipids and AA were different and depended on the growth phase of the fungus. The AA production was shown to be extremely sensitive to acidic pH values and was completely inhibited at a pH of 3.0. The optimum temperature for AA production was 20-22 • C. Continuous cultivation of M. alpina occurred in a glycerol-containing medium, and growth limitations were implemented through the addition of nitrogen and the selection of optimal conditions (pH 6.0, 20 • C). This ensured that active AA production occurred (25.2% of lipids and 3.1% of biomass), with the product yield from the consumed glycerol being 1.6% by mass and 3.4% by energy.

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Section: Introductionmentioning

confidence: 99%

The Effect of pH and Temperature on Arachidonic Acid Production by Glycerol-Grown Mortierella alpina NRRL-A-10995

et al. 2018

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“…Although the produced fatty acids were mainly accumulated in the cells without being secreted, there was no growth defect observed. Aligned with our work for metabolic engineering of Y. lipolytica to produce long-chain dicarboxylic acid (Abghari et al, 2017) and fatty alcohol (Wang et al, 2016), the current study further improved Y. lipolytica for production of long-chain (C16-C18) fatty acids.…”

Section: Discussionmentioning

confidence: 62%

Metabolic Engineering of Oleaginous Yeast Yarrowia lipolytica for Overproduction of Fatty Acids

2020

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The oleaginous yeast Yarrowia lipolytica has attracted much attention due to its ability to utilize a wide range of substrates to accumulate high lipid content and its flexibility for genetic manipulation. In this study, intracellular lipid metabolism in Y. lipolytica was tailored to produce fatty acid, a renewable oleochemical and precursor for production of advanced biofuels. Two main strategies, including blocking activation and peroxisomal uptake of fatty acids and elimination of biosynthesis of lipids, were employed to reduce fatty acid consumption by the native pathways in Y. lipolytica. Both genetic modifications improved fatty acid production. However, disruption of the genes responsible for assembly of nonpolar lipid molecules including triacylglycerols (TAGs) and steryl esters resulted in the deleterious effects on the cell growth. The gene tesA encoding thioesterase from Escherichia coli was expressed in the strain with disrupted faa genes encoding fatty acyl-CoA synthetases and pxa1 encoding peroxisomal acyl-CoA transporter, and the titer of fatty acids resulted in 2.3 g/L in shake flask culture, representing 11-fold improvement compared with the parent strain. Expressing the native genes encoding acetyl-CoA carboxylase (ACC) and hexokinase also increased fatty acid production, although the improvement was not as significant as that with tesA expression. Saturated fatty acids including palmitic acid (C16:0) and stearic acid (C18:0) increased remarkably in the fatty acid composition of the recombinant bearing tesA compared with the parent strain. The recombinant expressing tesA gene resulted in high lipid content, indicating the great fatty acid producing potential of Y. lipolytica. The results highlight the achievement of fatty acid overproduction without adverse effect on growth of the strain. Results of this study provided insight into the relationship between fatty acid and lipid metabolism in Y. lipolytica, confirming the avenue to reprogram lipid metabolism of this host for overproduction of renewable fatty acids.

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“…DCA can be synthesized in Y. lipolytica from hydrophobic substrate such n-alkane and fatty acids and are usually the products of bioconversion. Moreover, production of DCA from de novo synthesis has been recently described for the production of long chain dicarboxylic acid (LCDCA-16 and 18) using glycerol as the sole source of carbon [ 50 ] allowing the production of 0.3 g/L LCDCA in shake flask. In our study, we showed that the strain ∆pox FAS-I 1220 W eg DGAT can produce up to 0.47 ± 0.07 g/L MCDCA in shake flask which give to the strain a great potential and represents the first example to our knowledge of de novo synthesis of DCA with length from 10 to 14 carbons.…”

Section: Discussionmentioning

confidence: 99%

Increasing medium chain fatty acids production in Yarrowia lipolytica by metabolic engineering

et al. 2018

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BackgroundOleaginous yeast Yarrowia lipolytica is an organism of choice for the development of biofuel and oleochemicals. It has become a chassis for metabolic engineering in order to produce targeted lipids. Understanding the function of key-enzymes involved in lipid metabolism is essential to design better routes for enhanced lipid production and for strains producing lipids of interest. Because medium chain fatty acids (MCFA) are valuable compounds for biokerosene production, we previously generated strains capable of producing MCFA up to 12% of total lipid content (Rigouin et al. in ACS Synth Biol 6:1870–1879, 2017). In order to improve accumulation and content of C14 fatty acid (FA), the elongation, degradation and accumulation of these MCFA in Yarrowia lipolytica were studied.ResultsWe brought evidence of the role of YALI0F0654 (YlELO1) protein in the elongation of exogenous or de novo synthesized C14 FA into C16 FA and C18 FA. YlELO1 deletion into a αFAS_I1220W expressing strain leads to the sole production of C14 FA. However, because this strain does not provide the FA essential for its growth, it requires being cultivated with essential fatty acids and C14 FA yield is limited. To promote MCFA accumulation in Y. lipolytica without compromising the growth, we overexpressed a plant diglyceride acyltransferase specific for MCFA and reached an accumulation of MCFA up to 45% of total lipid content.ConclusionWe characterized the role of YlELO1 in Y. lipolytica by proving its involvement in Medium chain fatty acids elongation. We showed that MCFA content can be increased in Yarrowia lipolytica by promoting their accumulation into a stable storage form (triacylglycerides) to limit their elongation and their degradation.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-0989-5) contains supplementary material, which is available to authorized users.

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Combinatorial Engineering of Yarrowia lipolytica as a Promising Cell Biorefinery Platform for the de novo Production of Multi-Purpose Long Chain Dicarboxylic Acids

Cited by 20 publications

References 125 publications

The Effect of pH and Temperature on Arachidonic Acid Production by Glycerol-Grown Mortierella alpina NRRL-A-10995

The Effect of pH and Temperature on Arachidonic Acid Production by Glycerol-Grown Mortierella alpina NRRL-A-10995

Metabolic Engineering of Oleaginous Yeast Yarrowia lipolytica for Overproduction of Fatty Acids

Increasing medium chain fatty acids production in Yarrowia lipolytica by metabolic engineering

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