Understanding uptake and interconversion of omega-3 fatty acids by cultivated fish cells
Although fish are one of the best dietary sources of long-chain omega-3 fatty acids (FAs), these compounds are mostly bioaccumulated from a fish’s diet rather than synthesized de novo. Consistent with this, studies have found evidence of reduced omega-3 content in fish as a result of replacing fish-based feed with plant-based feed. Therefore, for cultivated fish to compete with conventionally-produced products, it will be necessary to identify cost-effective strategies for increasing the content of nutritionally-important omega-3 FAs in cultivated fish.
- Raw Materials, Ingredients, & Inputs
- Cell line development
- Cell culture media
- Host strain development
Freshwater fish tend to have less abundant sources of important, highly-unsaturated omega-3 FAs EPA and DHA in their diets. Likely as a result of this, rainbow trout and other freshwater or anadromous species are able to produce EPA and DHA from their precursor ALA, primarily in the liver (Tocher 2003). This is not true of many marine species, especially top predators, which are more dependent on dietary EPA and DHA. Consistent with the idea that marine fish obtain EPA, DHA, and other highly-unsaturated FAs from dietary sources, cultured bluefin tuna cells readily take up FAs added to the culture media, but this supplementation does not increase the concentrations of those FAs downstream in the biosynthetic pathway (Scholefield and Schuller 2014). Especially for marine species, cultivated fish may require direct supplementation with EPA and DHA, increasing the cost of production.
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To clarify the extent of the differences between species and between cell types, a systematic comparison of the ability of equivalent cell populations from muscle, fat, and liver of several freshwater and marine species to take up and interconvert purified ALA, EPA, and DHA would help. An exploration of the mechanisms by which the relevant desaturase and elongase genes are inactivated in marine fish cells and muscle cells as well as adipocytes of freshwater fish could lead to strategies for increasing conversion to EPA and DHA. Identification of methods (preferably non-GMO or at least non-integrating methods) by which these genes could be re-activated could allow for ALA to be converted to EPA and DHA at high rates within muscle cells or adipocytes or within cells from marine species which would otherwise be incapable of doing so. In order to increase omega-3 content by the most cost-effective and efficient means possible, it would be useful to test cells’ ability to take up omega-3 FAs from fewer highly purified plant or algal sources. Inputs rich in either ALA (e.g. flax seeds) or EPA and DHA (e.g. algae) might be appropriate depending on the ability of the cells in question to desaturate and elongate ALA.
Systematic research into omega-3 uptake and conversion will inform strategies for increasing the content of highly-unsaturated FAs including EPA and DHA within cultivated fish in a cost-effective manner. If desired, products could be produced with higher concentrations of these FAs than those found in conventionally-produced fish. Whereas much of the research described here falls into the category of basic knowledge generation, novel strategies for increasing expression of desaturase and elongase genes, as well as cost-effective purification schemes for FAs to be retained and taken up by cells with high efficiency, are fertile areas for generation of IP and might be attractive areas for R&D efforts within companies.
Integriculture’s CulNet system allows for media to be circulated between muscle and fat cells grown for cultivated meat and various types of support cells that can process waste products and/or produce necessary growth factors or other compounds. Liver cells, especially from freshwater fish, could be one type of support cell to produce highly unsaturated omega-3 FA’s to be taken up by cultured myocytes.
Supplementation of cultivated seafood with omega-3 fatty acids will require low-cost, animal-free sources of these compounds. Possible production platforms include large-scale algae farming, which is being pursued by companies like iWi, as well as production in plants. Camelina plants have been engineered using CRISPR to produce EPA and DHA and are being commercialized via a partnership between Yield10 Bioscience and Rothamsted Research.
State of the Industry Report: Cultivated Meat
This global analysis of the cultivated meat industry covers investments, consumer insights, and scientific progress in this growing market sector.
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