Download 1 and Method for the Production of Polyunsaturated Fatty Acids in

Name of product and/or technology
Nucleic Acid
and Method for the Production of Polyunsaturated Fatty Acids in Transgenic Organisms
Background
Fatty acids are carboxylic acids with long-chain hydrocarbon side groups that play a fundamental role in many
biological processes. They can be divided into two groups: saturated fatty acids, formed of single carbon bonds,
and unsaturated fatty acids, which contain one or more double carbon bonds. Unsaturated fatty acids are
produced by terminal desaturases which catalyze the formation of double bonds between the carbon atoms of a
fatty acid molecule.
Polyunsaturated fatty acids (PUFAs) have 2 to 6 double bonds and preferably from 18 to 24 carbon atoms in the
chain. Long chain PUFAs (LCPUFAs) have from 20 to 24 carbon atoms in the fatty acid chain. Generally, the
controlling steps in the production of LCPUFAs are catalyzed by membrane-associated fatty acid elongase
complexes. The complex consists of 4 components with different catalytic functions: the keto-acyl-CoA-5
synthase; the keto-acyl-CoA-reductase; the dehydratase; and the enoly-CoA-reductase.
LCPUFAs are essential components of cell membranes of various tissues and organelles in mammals. However,
mammals have a limited spectrum the enzymes required for the formation of particular double bonds in
unsaturated fatty acids and must take up these essential fatty acids via food. Starting with these precursors, the
physiologically important arachidonic acid (ARA), an ω6-fatty acid and the two ω3-fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic acid (DHA) are synthesized via a sequence of desaturase and elongase
reactions. EPA and DHA play a role in reducing our risk to cardiovascular disease and related precursor
conditions.
The major sources of PUFAs in human diet are oils from fish and algae but there is increasing demand for
alternative sources as the supply of fish oil is highly variable and the algal source of oil is expensive. Higher plants
comprise PUFAs such as linoleic acid and linolenic acid but do not have the necessary enzymes to catalyse the
elongation reaction for the production of LCPUFAs. The production of LCPUFAs in higher plants (preferably in oil
crops such as oilseed rape, linseed, sunflower and soybeans) would allow high-quality LCPUFAs to be
economically produced. A potential route is via recombinant methods, where genes which code for enzymes of
the biosynthesis of LCPUFAs are introduced and expressed into plants.
This patent takes research to the next level where marine equivalent EPA can be produced in a plant. As such
this is a major step forward.
Technology
The inventor has been involved with cutting-edge research focused on defining the molecular basis of LCPUFAs
biosynthetic pathway in marine microbes for over a decade and has successfully demonstrated the production
LCPUFAs in transgenic plants via iterative metabolic engineering. The present invention relates to a nucleic acid
derived from Perkinsus marinusi, an oyster protozoan parasite capable of synthesizing saturated and unsaturated
fatty acids, including ARA, via the [Delta]8-desaturase pathway. In this way the invention delivers high quality
EPA to the plant.
The nucleic acid encodes a [Delta]9-elongase, a [Delta]8-desaturase and a [Delta]5-desaturase enzyme; the
invention relates to the individual coding sequences and proteins encoded by these sequences as well as to a
process for converting linoleic acid to ARA. The coding sequences can be transcribed as a single transcript,
which simplifies the process of transforming cells required to express all three proteins, or as separate transcripts.
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Rothamsted Research
Reference: Patent 172
The nucleic acid sequence of the invention is linked with one or more regulatory sequences in the expression
cassette to enhance gene expression.
In a further aspect of the invention there is provided a transgenic non-human organism comprising at least one
nucleic acid, gene construct or vector according to the previous aspect of the invention. Host cells which are
suitable in principle for taking up the nucleic acid, the gene product and the vector according to the invention are
all prokaryotic or eukaryotic organisms. Hence, the constructs can advantageously be propagated in
microorganisms, in particular in E. coli and Agrobacterium tumefaciens, under selective conditions and make
possible the transfer of heterologous DNA into plants. Especially preferred plants according to the invention are
oil crops such as soybean, peanut, oilseed rape, canola, linseed, hemp, evening primrose, sunflower, safflower
and trees (oil palm, coconut).
Transgenic plants which comprise the polyunsaturated fatty acids synthesized in the process according to the
invention can advantageously be marketed directly without there being any need for the oils, lipids or fatty acids
synthesized to be isolated. Alternatively, the compounds produced in the process according to the invention can
also be isolated from the organisms, advantageously plants, in the form of their oils, fats, lipids and/or free fatty
acids. A further embodiment according to the invention is the use of the oil, lipid, the fatty acids and/or the fatty
acid composition in feedstuffs, foodstuffs, cosmetics or pharmaceuticals.
Patent Information
The patent is currently granted in China and is pending in India and Brazil.
Licensing Opportunities
Know-how licences and related consultancy opportunities are available in most countries. Licenses may be
exclusive, co-exclusive, non-exclusive or sole. Licenses will normally be for commercial purposes however
academic licenses are available. Rothamsted Research will retain the right to use the technology on its own
projects. Commercial Research and Development licenses containing an option to commercialise following
successful outcomes from a company’s R&D will also be considered.
Licensing
Richard Nugent (Ref. 172)
Rothamsted Research Ltd
Contracts & Intellectual Property
Harpenden
Email: [email protected]
Herts
Tel: +44 (0) 1582 763133 ext 2478
AL5 2JQ
United Kingdom
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