Metabolic

Tomatoes may turn out to be a brand new pure supply for Parkinson’s medicine

Scientists have made a tomato fortified with the Parkinson’s drug L-DOPA that could become a new, affordable source of one of the world’s most important medicines.

The development of the genetically modified tomato is having an impact on developing countries where access to medicines is restricted.

This novel use of tomato plants as a natural source of L-DOPA also provides benefits for people suffering from the adverse effects – including nausea and behavioral complications – from chemically synthesized L-DOPA.

Tomato – was selected as a widely used crop that can be used to increase production and potentially provides a standardized and controlled natural source of L-DOPA.

The team, led by the John Innes Center, modified the tomato fruit by introducing a gene responsible for synthesizing L-DOPA in beetroot and playing a role in the manufacture of betalain’s pigments.

L-DOPA is made from tyrosine, an amino acid found in many foods. The research team inserted a gene that codes for a tyrosinase, an enzyme that uses tyrosine to make molecules like L-DOPA. This increased L-DOPA levels specifically in the fruit portion of the plant and resulted in higher yields than those associated with L-DOPA production throughout the plant.

The levels achieved in the tomato fruits – 150 mg L-DOPA per kg tomatoes – were comparable to those observed in other L-DOPA accumulating plants – without some of the known disadvantages that previously hampered the plant’s metabolic production of the drug.

The aim now is to create a production pipeline in which L-DOPA is extracted from the tomatoes and purified into a pharmaceutical product.

The idea is that you can grow tomatoes with relatively little infrastructure. As GMOs (genetically modified organisms), you could grow them in sieve houses, controlled environments with very tight meshes, to prevent pollen from escaping through insects.

Then you can scale at a relatively low cost. A local industry could make L-DOPA from tomatoes because it is soluble and you can do extractions. Then you could make a relatively low tech purified product that could be dispensed locally. “

Professor Cathie Martin (FRS), corresponding author of the study

Parkinson’s disease is a growing problem in developing countries where many people cannot afford the $ 2 daily price for synthetic L-DOPA.

L-DOPA is an amino acid precursor to neurochemical dopamine and is used to compensate for the depleted dopamine supply in Parkinson’s patients.

L-DOPA, also known as levodopa, has been the gold standard therapy for Parkinson’s disease since its introduction as a drug in 1967. It is one of the major pharmaceuticals declared by the World Health Organization (WHO) and its market value is hundreds of billions of dollars.

The most common form of the drug is made by chemical synthesis, but natural sources are also available. Few plants have been reported to contain measurable amounts of the molecule, mainly in seeds.

The velvet bean Mucuna pruriens, the seeds of which contain up to 10% L-DOPA, has been studied the most. However, this is problematic because the plant is covered in urticating hairs that contain mucus which can cause irritation and allergic reactions to field workers who harvest the crops. The beans themselves cause increased tryptamine levels, which can cause hallucinations in Parkinson’s patients.

“We have shown that it is possible to use the tyrosinase-expressing tomatoes as a source of L-DOPA. This is another demonstration of tomatoes as a powerful option for synthetic biology. In addition, there have been surprising positive effects, including an improvement in shelf life and elevated amino acid levels that we can study, “says lead author Dr. Dario Breitel.

Source:

Journal reference:

Breitel, D., et al. (2020) Metabolic Engineering of L-DOPA Enriched Tomato Fruit. Metabolic Engineering. doi.org/10.1016/j.ymben.2020.11.011.

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