Metabolic engineered tomatoes to produce L-DOPA
Technology reference: J20CM1
Proposed use
L-DOPA, also known as Levodopa or L-3,4-dihydroxyphenylalanine, is a non-standard amino acid, and the gold standard drug for the treatment for Parkinson’s Disease (PD).
This technology enables production and ready extraction of naturally sourced L-DOPA from genetically modified tomatoes.
Scaling up production can be done at relatively low cost without specialised equipment.
A local industry could prepare L-DOPA from tomato fruit because this compound is water-soluble and easy to extract. This enables a purified product which could be dispensed locally, without consumption of the rest of the GM tomato.
Problem addressed
The most common form of L-DOPA is produced by chemical synthesis, but this requires an expensive catalyst and infrastructures not available throughout the world.
Natural sources are also available. Only a few plants have been reported to contain measurable quantities of the molecule, mainly in seeds.
The most studied is the velvet bean (Mucuna pruriens), which contains up to 10% L-DOPA in its seeds. But this is problematic because the plant is covered in urticating hairs that contain mucunain that can cause irritation and allergic reactions in field workers who harvest the crop.
The beans themselves contain high levels of tryptamines that can cause hallucinations in Parkinson’s disease patients.
Transgenic tomato fruit producing L-DOPA provide an easily scalable alternative source of this important pharmaceutical in a form that is easy to extract without specialist equipment.
L-DOPA tomatoes could represent a cheap alternative to chemically synthesised L-DOPA for those who cannot afford the daily $2 cost in parts of the world without access to pharmaceutical synthesis capabilities.
Benefits
- Affordable source of Parkinson’s disease drug L-DOPA
- Sustainable production of L-DOPA without infrastructure necessary for pharmaceutical synthesis
- L-DOPA is produced in tomato fruit enabling low-cost extraction
- Shelf-life properties of the fruit were improved
- Improved fruit firmness post-harvest, and reduced susceptibility to the necrotropic fungus Botrytis cinerea
Technology Overview
BvCYP76AD6 is a gene encoding the enzyme that is responsible for L-DOPA synthesis from tyrosine, as a precursor of the coloured pigment group betalains, in beetroot.
When this gene is overexpressed in tomato plants in a fruit specific manner, L-DOPA accumulates.
The co-expression of the metabolic master regulator MYB12, together with BvCYP76AD6, also specifically in tomato fruit, increases the L-DOPA levels further.
The extraction of the soluble L-DOPA from tomatoes is low-tech. Purification can be achieved directly in tomato juice with added ascorbate to prevent the oxidation of L-DOPA, followed by chromatographic separation such as thin layer chromatography.
Intellectual property information
Pending PCT Application (unpublished) – “Metabolic engineering of plants enriched in L-DOPA”.
Published paper(s)
Breitel, D., Brett, P., Alseekh, S., Fernie, A. R., Butelli, E., and Martin, C. (2020). ‘Metabolic engineering of tomato fruit enriched in L-DOPA. Metabolic Engineering‘
Inventor information
- Dr Dario Breitel – Alumni from the Martin laboratory currently with Plantae Bioscience Ltd
- Dr Eugenio Butelli – Postdoctoral researcher in the Martin laboratory at the John Innes Centre
- Professor Cathie Martin – Group leader at the John Innes Centre and Fellow of the Royal Society whose research interests lie in using plant science to improve human diet and health