Direct production of fatty alcohols from glucose using engineered strains of Yarrowia lipolytica

Cordova, Lauren T.; Butler, Jonathan; Alper, Hal S.

doi:10.1016/j.mec.2019.e00105

Cited by 46 publications

(39 citation statements)

References 31 publications

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“…Similar to the case with S. cerevisiae greater than 90% of the product fatty alcohols were retained in the cells (636.9 mg L −1 intracellular vs 53.3 mg L −1 extracellular) (Wang G. et al, 2016). The addition of dodecane to the growth medium increased the proportion of fatty alcohol found extracellularly (Wang W. et al, 2016;Cordova et al, 2020). The addition of dodecane also increased the total fatty alcohol titer suggesting that retention of the product in the cells was inhibiting biosynthesis (Wang G. et al, 2016).…”

Section: Engineering Fatty Alcohol Production In Oleaginous Yeastssupporting

confidence: 55%

Biosynthesis of Fatty Alcohols in Engineered Microbial Cell Factories: Advances and Limitations

Krishnan

McNeil

Stuart

2020

Front. Bioeng. Biotechnol.

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Concerns about climate change and environmental destruction have led to interest in technologies that can replace fossil fuels and petrochemicals with compounds derived from sustainable sources that have lower environmental impact. Fatty alcohols produced by chemical synthesis from ethylene or by chemical conversion of plant oils have a large range of industrial applications. These chemicals can be synthesized through biological routes but their free forms are produced in trace amounts naturally. This review focuses on how genetic engineering of endogenous fatty acid metabolism and heterologous expression of fatty alcohol producing enzymes have come together resulting in the current state of the field for production of fatty alcohols by microbial cell factories. We provide an overview of endogenous fatty acid synthesis, enzymatic methods of conversion to fatty alcohols and review the research to date on microbial fatty alcohol production. The primary focus is on work performed in the model microorganisms, Escherichia coli and Saccharomyces cerevisiae but advances made with cyanobacteria and oleaginous yeasts are also considered. The limitations to production of fatty alcohols by microbial cell factories are detailed along with consideration to potential research directions that may aid in achieving viable commercial scale production of fatty alcohols from renewable feedstock.

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Section: Engineering Fatty Alcohol Production In Oleaginous Yeastssupporting

confidence: 55%

Biosynthesis of Fatty Alcohols in Engineered Microbial Cell Factories: Advances and Limitations

Krishnan

McNeil

Stuart

2020

Front. Bioeng. Biotechnol.

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“…A fatty alcohol titer of 6.33 g/L was achieved in fed-batch fermentation in E. coli via the deletion of all fatty acyl-CoA thioestarases and ldhA , pta , and ackA genes, to starve cells of fatty acids and remove competing pathways ( Liu et al, 2016 ). The expression of Tyto alba FAR (TaFAR1) in Y. lipolytica resulted in the production of 690 mg/L of hexadecan-1-ol ( Wang G. et al, 2016 ), while the Y. lipolytica transformed with the MhFAR gene encoding the reductase from Marinobacter hydrocarbonoclasticus produced 6 g/L of alcohols representing an accumulation of 36 mg alcohols/g of cells ( Cordova et al, 2019 ). The same reductase stimulated the production of 770 mg/L of fatty alcohols in L. starkeyi ( Wang W. et al, 2016 ) and 8 g/L of fatty alcohols in Rhodosporidium toruloides ( Fillet et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…The properties and the potential applications of fatty alcohol depend on their molecular structure. Generally, fatty alcohols are used as fuels, solvents, detergents, cosmetics, lubricants, and pharmaceuticals, or may serve as precursors for other compounds such as waxes or polymers ( Rutter and Rao, 2016 ; Wang G. et al, 2016 ; Wang W. et al, 2016 ; Borodina et al, 2018a ; Cordova et al, 2019 ). In 2019, the global demand for fatty alcohols was estimated to be over two million tons, with an annual growth rate of 4.3%.…”

Section: Introductionmentioning

confidence: 99%

“…In 2019, the global demand for fatty alcohols was estimated to be over two million tons, with an annual growth rate of 4.3%. Traditionally, these molecules are produced through the catalytic hydrogenation of petrochemicals or plant oils, which currently relies on fossil fuels or unsustainable palm farming and has significant environmental consequences such as deforestation or contribution to global warming ( Rutter and Rao, 2016 ; Shah et al, 2016 ; Cordova et al, 2019 ). Therefore, there is an urgent requirement for a further efficient and ecologically-friendly process.…”

Section: Introductionmentioning

confidence: 99%

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Production of Long Chain Fatty Alcohols Found in Bumblebee Pheromones by Yarrowia lipolytica

Hambalko

Gajdoš

Nicaud

et al. 2021

Front. Bioeng. Biotechnol.

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Fatty alcohols (FA-OH) are aliphatic unbranched primary alcohols with a chain of four or more carbon atoms. Besides potential industrial applications, fatty alcohols have important biological functions as well. In nature, fatty alcohols are produced as a part of a mixture of pheromones in several insect species, such as moths, termites, bees, wasps, etc. In addition, FA-OHs have a potential for agricultural applications, for example, they may be used as a suitable substitute for commercial insecticides. The insecticides have several drawbacks associated with their preparation, and they exert a negative impact on the environment. Currently, pheromone components are prepared mainly through the catalytic hydrogenation of plant oils and petrochemicals, which is an unsustainable, ecologically unfriendly, and highly expensive process. The biotechnological production of the pheromone components using engineered microbial strains and through the expression of the enzymes participating in the biosynthesis of these components is a promising approach that ensures ecological sustenance as well. The present study was aimed at evaluating the production of FA-OHs in the oleaginous yeast, Yarrowia lipolytica, with different lengths of fatty-acyl chains by expressing the fatty acyl-CoA reductase (FAR) BlapFAR4 from B. lapidarius, producing C16:0-OH, C16:1Δ9-OH, and lower quantities of both C14:0-OH and C18:1Δ9-OH, and BlucFAR1 from B. lucorum, producing FA-OHs with a chain length of 18–26 carbon atoms, in this yeast. Among the different novel Y. lipolytica strains used in the present study, the best results were obtained with JMY7086, which carried several lipid metabolism modifications and expressed the BlucFAR1 gene under the control of a strong constitutive promoter 8UAS-pTEF. JMY7086 produced only saturated fatty alcohols with chain lengths from 18 to 24 carbon atoms. The highest titer and accumulation achieved were 166.6 mg/L and 15.6 mg/g DCW of fatty alcohols, respectively. Unlike JMY7086, the BlapFAR4-expressing strain JMY7090 produced only 16 carbon atom-long FA-OHs with a titer of 14.6 mg/L.

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“…94 enzyme variants were screened, and FAR from M. aquaeolei VT8 (Maqu_220) and the engineered strain produced 1.5 and 5.8g/L total fatty alcohols in shake flask and 2L bioreactor, respectively. 95 Furthermore, fatty alcohol production was also achieved in photosynthetic organism, cyanobacteria Synechocystis sp. PCC 6803 by heterologous expression of a FAR gene from M. aquaeolei VT8, which resulted in 0.39 ± 0.06 mg/g dry cell weight (dcw) of fatty alcohol.…”

Section: Fusarium Fujikuroimentioning

confidence: 99%

Recent advances in domesticating non‐model microorganisms

Fatma

Schultz

Zhao

2020

Biotechnology Progress

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Non-model microorganisms have been increasingly explored as microbial cell factories for production of chemicals, fuels, and materials owing to their unique physiology and metabolic capabilities. However, these microorganisms often lack facile genetic tools for strain development, which hinders their adoption as production hosts. In this review, we describe recent advances in domestication of non-model microorganisms, including bacteria, actinobacteria, cyanobacteria, yeast, and fungi, with a focus on the development of genetic tools. In addition, we highlight some successful applications of non-model microorganisms as microbial cell factories.

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Direct production of fatty alcohols from glucose using engineered strains of Yarrowia lipolytica

Cited by 46 publications

References 31 publications

Biosynthesis of Fatty Alcohols in Engineered Microbial Cell Factories: Advances and Limitations

Biosynthesis of Fatty Alcohols in Engineered Microbial Cell Factories: Advances and Limitations

Production of Long Chain Fatty Alcohols Found in Bumblebee Pheromones by Yarrowia lipolytica

Recent advances in domesticating non‐model microorganisms

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