Dataset Information

De novo production of resveratrol from glycerol by engineering different metabolic pathways in Yarrowia lipolytica.

ABSTRACT: Resveratrol is a polyphenol with multiple applications in pharma, cosmetics and food. The aim of this study was to construct Yarrowia lipolytica strains able to produce resveratrol. For this purpose, resveratrol-biosynthesis genes from bacteria and plants were expressed in this host. Since resveratrol can be produced either via tyrosine or phenylaniline, both pathways were tested, first with a single copy and then with two copies. The phenylalanine pathway resulted in slightly higher production in glucose media, although when the media was supplemented with amino acids, the best production was found in the strain with two copies of the tyrosine pathway, which reached 0.085 ?g/L. When glucose was replaced by glycerol, a preferred substrate for bioproduction, the best results, 0.104 ?g/L, were obtained in a strain combining the expression of the two synthesis pathways. Finally, the best producer strain was tested in bioreactor conditions where a production of 0.43 ?g/L was reached. This study suggests that Y. lipolytica is a promising host for resveratrol production from glycerol.

SUBMITTER: He Q

PROVIDER: S-EPMC7522117 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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De novo production of resveratrol from glycerol by engineering different metabolic pathways in <i>Yarrowia lipolytica</i>.

He Qin Q Szczepańska Patrycja P Yuzbashev Tigran T Lazar Zbigniew Z Ledesma-Amaro Rodrigo R

Metabolic engineering communications 20200919

Resveratrol is a polyphenol with multiple applications in pharma, cosmetics and food. The aim of this study was to construct <i>Yarrowia lipolytica</i> strains able to produce resveratrol. For this purpose, resveratrol-biosynthesis genes from bacteria and plants were expressed in this host. Since resveratrol can be produced either via tyrosine or phenylaniline, both pathways were tested, first with a single copy and then with two copies. The phenylalanine pathway resulted in slightly higher prod ...[more]

PMID: 33014707

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Project description:BackgroundSugar alcohols are widely used as low-calorie sweeteners in the food and pharmaceutical industries. They can also be transformed into platform chemicals. Yarrowia lipolytica, an oleaginous yeast, is a promising host for producing many sugar alcohols. In this work, we tested whether heterologous expression of a recently identified sugar alcohol phosphatase (PYP) from Saccharomyces cerevisiae would increase sugar alcohol production in Y. lipolytica.ResultsY. lipolytica was found natively to produce erythritol, mannitol, and arabitol during growth on glucose, fructose, mannose, and glycerol. Osmotic stress is known to increase sugar alcohol production, and was found to significantly increase erythritol production during growth on glycerol. To better understand erythritol production from glycerol, since it was the most promising sugar alcohol, we measured the expression of key genes and intracellular metabolites. Osmotic stress increased the expression of several key genes in the glycerol catabolic pathway and the pentose phosphate pathway. Analysis of intracellular metabolites revealed that amino acids, sugar alcohols, and polyamines are produced at higher levels in response to osmotic stress. Heterologous overexpression of the sugar alcohol phosphatase increased erythritol production and glycerol utilization in Y. lipolytica. We further increased erythritol production by increasing the expression of native glycerol kinase (GK), and transketolase (TKL). This strain was able to produce 27.5 ± 0.7 g/L erythritol from glycerol during batch growth and 58.8 ± 1.68 g/L erythritol during fed-batch growth in shake-flasks experiments. In addition, the glycerol utilization was increased by 2.5-fold. We were also able to demonstrate that this strain efficiently produces erythritol from crude glycerol, a major byproduct of the biodiesel production.ConclusionsWe demonstrated the application of a promising enzyme for increasing erythritol production in Y. lipolytica. We were further able to boost production by combining the expression of this enzyme with other approaches known to increase erythritol production in Y. lipolytica. This suggest that this new enzyme provides an orthogonal route for boosting production and can be stacked with existing designs known to increase sugar alcohol production in yeast such as Y. lipolytica. Collectively, this work establishes a new route for increasing sugar alcohol production and further develops Y. lipolytica as a promising host for erythritol production from cheap substrates such as glycerol.

Dataset Information

De novo production of resveratrol from glycerol by engineering different metabolic pathways in Yarrowia lipolytica.

Publications

De novo production of resveratrol from glycerol by engineering different metabolic pathways in <i>Yarrowia lipolytica</i>.

Similar Datasets

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