Abstract
The omega-3 fatty acids, cis-5, 8, 11, 14, and 17-eicosapentaenoic acid (C20:5; EPA) and cis-4, 7, 10, 13, 16, and 19-docosahexaenoic acid (C22:6; DHA), have wide-ranging benefits in improving heart health, immune function, mental health, and infant cognitive development. Currently, the major source for EPA and DHA is from fish oil, and a minor source of DHA is from microalgae. With the increased demand for EPA and DHA, DuPont has developed a clean and sustainable source of the omega-3 fatty acid EPA through fermentation using metabolically engineered strains of Yarrowia lipolytica. In this mini-review, we will focus on DuPont’s technology for EPA production. Specifically, EPA biosynthetic and supporting pathways have been introduced into the oleaginous yeast to synthesize and accumulate EPA under fermentation conditions. This Yarrowia platform can also produce tailored omega-3 (EPA, DHA) and/or omega-6 (ARA, GLA) fatty acid mixtures in the cellular lipid profiles. Fundamental research such as metabolic engineering for strain construction, high-throughput screening for strain selection, fermentation process development, and process scale-up were all needed to achieve the high levels of EPA titer, rate, and yield required for commercial application. Here, we summarize how we have combined the fundamental bioscience and the industrial engineering skills to achieve large-scale production of Yarrowia biomass containing high amounts of EPA, which led to two commercial products, New Harvest™ EPA oil and Verlasso® salmon.
Highlights
Omega-3 fatty acids refer to the long-chain polyunsaturated fatty acids (LCPUFA) with the first C=C double bond at the n-3 position, i.e., the third carbon from the methyl end of the carbon chain
Integration of a single copy of these four gene expression cassettes into the genome of Y. lipolytica strain American Type Culture Collection (ATCC) #20362 resulted in the synthesis of EPA at about 3 % of the total fatty acid methyl esters (FAME), with 34 % of all fatty acids derived from the engineered pathway, and the majority was GLA (Zhu et al 2010)
The Y. lipolytica yeast was engineered in DuPont to produce a high level of EPA in biomass under commercial-scale fermentation conditions
Summary
Omega-3 fatty acids refer to the long-chain polyunsaturated fatty acids (LCPUFA) with the first C=C double bond at the n-3 position, i.e., the third carbon from the methyl end of the carbon chain. Introduction of either the Δ6 or Δ9 pathway genes into the wild-type strain should allow the production of EPA through desaturation and elongation of the native fatty acid species. Scientists were trying to use it as a host for efficient secretion of expressed heterologous proteins
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