Genetically modified tomato

GM tomatoes could offer source of essential medication

Image credit: Phil Robinson

Scientists from the John Innes Centre in Norwich have engineered a tomato enriched in the Parkinson’s disease drug L-DOPA, potentially rendering one of the world’s most essential medications more accessible and affordable.

The researchers selected the tomato, due to it being a widely cultivated crop which could potentially offer a standardised and controlled source of L-DOPA.

L-DOPA is an amino acid precursor of dopamine. As a drug (Levodopa), it is is used to treat Parkinson’s disease and some other movement disorders, compensating for the depleted supply of dopamine in patients. It is classified as an essential medication by the WHO.

The most common form of the drug is produced by chemical synthesis, but some people suffer adverse effects from synthesised L-DOPA, including nausea and behavioural complications. Only a handful of plants have been found to contain measurable quantities of the molecule, mainly in their seeds.

In order to create an alternative plant source of L-DOPA, the researchers modified the tomato by introducing a gene responsible for the synthesis of L-DOPA in beetroot. L-DOPA is produced from tyrosine, so the researchers inserted a gene encoding tyrosinase: an enzyme which uses tyrosine to build molecules including L-DOPA. This elevated the level of L-DOPA in the fruit part of the tomato plant, leading to higher yields.

The researchers achieved L-DOPA levels of 150mg/kg of tomato fruit; these levels are comparable to those observed in other L-DOPA accumulating plants, but without some of the known drawbacks which have hampered plant metabolic production of the substance previously.

“The idea is that you can grow tomatoes with relatively little infrastructure,” said Professor Cathie Martin, co-author of the study. “As GMOs, you could grow them in screen houses - controlled environments with very narrow meshes - so you would not have pollen escape through insects.

“Then you could scale up at relatively low cost. A local industry could prepare L-DOPA from tomatoes because it’s soluble and you can do extractions. Then you could make a purified product relatively low tech, which could be dispensed locally.”

The researchers aim to establish a production pipeline for extracting L-DOPA from the genetically-modified tomatoes and purifying it into the pharmaceutical product. This could be particularly valuable in areas where access to pharmaceuticals is restricted.

First author Dario Breitel commented: “We have demonstrated that the use of the tyrosinase-expressing tomatoes as a source of L-DOPA is possible. It’s a further demonstration of tomato as a strong option for synthetic biology. Additionally, there were surprising beneficial effects including improvement in shelf-life and raised levels of amino-acids that we can investigate.”

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