Industry races to get green, GM omega-3 from plants

By Stephen Daniells

- Last updated on GMT

Related tags Fatty acids Fatty acid Omega-3 fatty acid

Industry giants are locked in a "fish oil arms race" to develop genetically modified crops that could challenge the supremacy of fish as the best source of omega-3 fatty acid, with both BASF and DuPont reporting progress in the field.

Fears about dwindling fish stocks, coupled with the putative risk of pollutants from oily fish, have pushed some in academia and industry to investigate the extraction of omega-3 from alternative sources.

Docosahexaenoic acid (DHA) extracted from non-GM microalgae is already on the market, as is plant-source alpha-linolenic acid (ALA), a shorter chain omega-3 that is less bioavailable for humans.

But it is thought that other plants like soybeans and Brassica could offer a sustainable and pollutant-free source of eicosapentaenoic acid (EPA) as well as DHA - assuming the genetically modified tag that comes along with the source is accepted by consumers. The principle is to add genes that convert shorter chain omega-3 and omega-6 fatty acids, found naturally in the plants, into more bioavailable longer chain fatty acids.

DuPont, one of the major movers and shakers in this area, revealed last week that it has developed a transgenic soybean with a long-chain omega-3 content of 40 per cent, and is heading for field testing of the crop. DuPont's focus has been on maximising both EPA and DHA, and scientists based at the DuPont Experimental Station in Delaware have expanded the standard procedure of desaturating and elongating the shorter chain fatty acids by using co-expression of an additional enzyme, omega-3 microsomal desaturase from the fungus Saprolegnia diclina​, to convert the omega-6 very long chain polyunsaturated fatty acids (VLC-PUFAs) into omega-3s.

Anthony Kinney from Dupont told attendees at the 17th International Symposium on Plant Lipids that the company has achieved "target long-chain PUFA contents up to 40 weight per cent of the oil of homozygous soybean seeds."

BASF, meanwhile, is an industrial partner the EU-sponsored LIPGENE project, an EU Sixth Framework Programme Integrated Project made up of a consortium of 25 research laboratories across Europe, including Trinity College Dublin, University of Reading, University of Oslo.

Johnathan Napier, a professor of Crop Performance and Improvement (CPI) from Rothamsted Research and member of the LIPGENE project, told that crops producing EPA have already been developed that exceed fatty acid levels found in fish (between 10 and 20 per cent). Professor Napier said that the main crops being looked at by LIPGENE include linseed, soybean, Arabidopsis plants, Brassica juncea​, and oilseed rape.

The science behind the crops consists of inserting genes into the plant genome that will encode for addition chemical steps in fatty acid production in the plant. Crops such as linseed are a naturally rich source of omega-3 fatty acid ALA - a precursor to the longer chain EPA and DHA - as well as the omega-6 fatty acid arachidonic acid (AA) - a precursor for the longer chain omega-6 fatty acids. To transform ALA to EPA and then further to DHA, genes are required that encode for the desaturation of ALA (by the enzyme, delta6-desaturase) to form stearidonic acid (SDA).

An enzyme (malonyl co-enzyme A) then elongates the SDA from an 18-carbon chain to a 20-carbon chain, and further desaturation, this time by the delta5-desaturase enzyme, results in the production of EPA. For DHA production, two more genes are needed for further elongation and desaturation, making DHA a significantly bigger challenge for scientists. The enzymes which act to desaturate and elongate the fatty acids also work on the omega-6 fatty acids found in plants, with linoleic acid converted to gamma-linolenic acid (GLA) and then to arachinodonic acid (ARA).

The first report of EPA accumulation was made in 2004 in transgenic Arabidopsis plants, with a level of 3.0 per cent obtained. ARA levels were measured at 6.6 per cent (Nat Biotechnology​, Vol 22, pp 739-745). Brassica juncea​ plants have also reported positive and promising results. A recent study (Nat Biotechnology​, 2005, Vol 23, pp 1013-1017) reported ARA and EPA accumulation of 25 and 15 per cent respectively. "B. juncea is a highly efficient host for the synthesis of ARA and EPA to high levels,"​ wrote Professor Napier in Physiologia Plantarum​. But the news has not all been good. Linseed, considered an ideal crop because it contains naturally high concentrations of ALA, proved disappointing when the transgenic plants were produced. It was found that, while production of the omega-3 and omega-6 intermediates SDA and GLA, averaged over 25 per cent, the subsequent longer chain EPA and ARA was only formed in small quantities.

The reason behind the disappointing end concentrations of EPA, explained Professor Napier, is the endogenous biochemistry of the linseed that limits production of the elongated omega-3 fatty acid. "Thus, although linseed was chosen as a suitable host for the reverse-engineering of omega-3 very long chain polyunsaturated fatty acids (VLC-PUFAs) on the basis of very high levels of the precursor ALA, endogenous channelling activities hindered the accumulation of omega-3 fatty acids such as EPA,"​ wrote Professor Napier in a recent review of the subject (Physiologia Plantarum​, 2006, Vol 126, pp 398-406). In other words, linseed "doesn't work."

DuPont and BASF are the main two players in this field, and the two companies are locked, said Napier, in a "fish oil arms race."​ But the field is not closed to others, with Monsanto focussing its research on GM canola crops that produce SDA, the intermediate between ALA and EPA. The reason for this, said Napier, is that it easier to make SDA than to go all the way to EPA and, eventually, DHA. Using genes isolated from the commercially grown fungus Mortierella alpina​, Monsanto has reported SDA accumulation of about 16 per cent of total fatty acid content (Journal of Nutrition​, Vol 133, pp 4271-4274).

While EPA levels have been creeping steadily upwards, subsequent production of DHA has only been reported in small quantities. The main remaining biotechnological challenge, according to Napier, is to go from EPA to significant production of DHA in the crops. "That will take a technological leap forward,"​ said Napier.

The other major challenge is for consumer acceptance of omega-3 from genetically modified crop sources. "This is the conundrum,"​ said Napier. "You have the health benefits of omega-3 coming from a sustainable source, but on the flip side the crops are GM.""It will be interesting to see how it pans out."

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