A metabolic engineering strategy for producing conjugated linoleic acids using the oleaginous yeast Yarrowia lipolytica

Imatoukene, Nabila; Verbeke, Jonathan; Béopoulos, Athanasios; Taghki, Abdelghani Idrissi; Thomasset, Brigitte; Sarde, Claude-Olivier; Nonus, M.; Nicaud, Jean‐Marc

doi:10.1007/s00253-017-8240-6

Cited by 46 publications

(22 citation statements)

References 43 publications

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“…The engineered strain produced polyhydroxyalkanoate at 2.84% of DCW in YNBD medium containing 1.0% OA and 1.11 g L À1 of PHA (21.9 g L À1 DCW) after 72 h cultivation in YNBD medium containing triolein. [79,80] In order to construct a biosynthetic pathway for γ-linolenic acid (C18:3, n-6, GLA) in Y. lipolytica, the Δ12 desaturase and Δ6 desaturase genes from M. alpina were co-overexpressed under the control of the strong hp4d promoter. Unsaturated fatty acids such as OA and LA can be naturally synthesized by Y. lipolytica.…”

Section: Lipid-derived Chemicalsmentioning

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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Section: Lipid-derived Chemicalsmentioning

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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“…Of the several microbial hosts used in such systems, the oleaginous yeast Y. lipolytica is the most studied and has been engineered to produce large amounts of lipids and lipid derivatives, such as ricinoleic acid (Beopoulos et al, 2014), conjugated linoleic acids (Imatoukene et al, 2017), cyclopropane FAs (Czerwiec et al, 2019), and cocoa butter-like oils (Papanikolaou et al, 2003). Y. lipolytica can naturally grow in a broad range of substrates and has been further engineered to use even more substrates .…”

Section: Introductionmentioning

confidence: 99%

De novo Biosynthesis of Odd-Chain Fatty Acids in Yarrowia lipolytica Enabled by Modular Pathway Engineering

Park

Ledesma-Amaro

Nicaud

2020

Front. Bioeng. Biotechnol.

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Microbial oils are regarded as promising alternatives to fossil fuels as concerns over environmental issues and energy production systems continue to mount. Odd-chain fatty acids (FAs) are a type of valuable lipid with various applications: they can serve as biomarkers, intermediates in the production of flavor and fragrance compounds, fuels, and plasticizers. Microorganisms naturally produce FAs, but such FAs are primarily even-chain; only negligible amounts of odd-chain FAs are generated. As a result, studies using microorganisms to produce odd-chain FAs have had limited success. Here, our objective was to biosynthesize odd-chain FAs de novo in Yarrowia lipolytica using inexpensive carbon sources, namely glucose, without any propionate supplementation. To achieve this goal, we constructed a modular metabolic pathway containing seven genes. In the engineered strain expressing this pathway, the percentage of odd-chain FAs out of total FAs was higher than in the control strain (3.86 vs. 0.84%). When this pathway was transferred into an obese strain, which had been engineered to accumulate large amounts of lipids, odd-chain fatty acid production was 7.2 times greater than in the control (0.05 vs. 0.36 g/L). This study shows that metabolic engineering research is making progress toward obtaining efficient cell factories that produce odd-chain FAs.

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“…The yeast Yarrowia lipolytica has been the most studied yeast for lipid production . This yeast has been the subject of genetic and metabolic engineering, allowing researchers to obtain significant amounts of oil showing desirable profiles of PUFA . However, several other yeast species have been researched in order to expand the possibilities of PUFA production, such as strains of Lipomyces starkeyi , Rhodosporidium toruloides , Rhodotorula glutinis , Candida curvatus , and Cryptococcus curvatus , which have been intensively studied regarding the optimization of their cultivation conditions and genetic modifications .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10] This yeast has been the subject of genetic and metabolic engineering, allowing researchers to obtain significant amounts of oil showing desirable profiles of PUFA. [11][12][13] However, several other yeast species have been researched in order to expand the possibilities of PUFA production, such as strains of Lipomyces starkeyi, Rhodosporidium toruloides, Rhodotorula glutinis, Candida curvatus, and Cryptococcus curvatus, which have been intensively studied regarding the optimization of their cultivation conditions and genetic modifications. 1,8,[14][15][16] The nonpathogenic, ascomycete yeast Meyerozyma guilliermondii, previously known as Pichia guilliermondii, has been reported as an oleaginous strain.…”

Section: Introductionmentioning

confidence: 99%

Oleaginous yeast Meyerozyma guilliermondii shows fermentative metabolism of sugars in the biosynthesis of ethanol and converts raw glycerol and cheese whey permeate into polyunsaturated fatty acids

Fabricio

Valente

Ayub

2019

Biotechnology Progress

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We studied the biotechnological potential of the recently isolated yeast Meyerozyma guilliermondii BI281A to produce polyunsaturated fatty acids and ethanol, comparing products yields using glucose, raw glycerol from biodiesel synthesis, or whey permeate as substrates. The yeast metabolism was evaluated for different C/N ratios (100:1 and 50:1). Results found that M. guilliermondii BI281A was able to assimilate all tested substrates, and the most efficient conversion obtained was observed using raw glycerol as carbon source (C/N ratio 50:1), concerning biomass formation (5.67 g·L−1) and lipid production (1.04 g·L−1), representing 18% of dry cell weight. Bioreactors experiments under pH and aeration‐controlled conditions were conducted. Obtained fatty acids were composed of ~67% of unsaturated fatty acids, distributed as palmitoleic acid (C16:1, 9.4%), oleic acid (C18:1, 47.2%), linoleic acid (C18:2 n−6, 9.6%), and linolenic acid (C18:3 n−3, 1.3%). Showing fermentative metabolism, which is unusual for oleaginous yeasts, M. guilliermondii produced 13.7 g·L−1 of ethanol (yields of 0.27) when growing on glucose medium. These results suggest the promising use of this uncommonly studied yeast to produce unsaturated fatty acids and ethanol using cheap agro‐industrial residues as substrates in bioprocess.

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A metabolic engineering strategy for producing conjugated linoleic acids using the oleaginous yeast Yarrowia lipolytica

Cited by 46 publications

References 43 publications

Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction

Recent Advances in Metabolic Engineering of Yarrowia lipolytica for Lipid Overproduction

De novo Biosynthesis of Odd-Chain Fatty Acids in Yarrowia lipolytica Enabled by Modular Pathway Engineering

Oleaginous yeast Meyerozyma guilliermondii shows fermentative metabolism of sugars in the biosynthesis of ethanol and converts raw glycerol and cheese whey permeate into polyunsaturated fatty acids

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