Summary of: metabolic engineering of tomato fruit enriched in L-DOPA, paper by Breitel et al. (2020)
Part of learning about Parkinson's disease is keeping up with new research articles. Here we'll be summarizing and breaking down a paper by Breitel et al. (2020) titled Metabolic engineering of tomato fruit enriched in L-DOPA.
In this manuscript, the authors wanted to explore the production of L-dopa in plants that don't naturally carry it, through genetic engineering. Βy forcing these plants to produce L-dopa, it would allow for a larger quantity of the drug that can be used for medicinal treatments.
What is L-dopa?
Levodopa (L-dopa) is a metabolite synthesized from the amino acid tyrosine. It has high concentrations of antioxidant properties and is a precursor for epinephrine and codeine which is a naturally produced hormone and an opioid, respectfully. L-dopa is a commonly prescribed medication for PD.
How is L-dopa connected to PD?
L-dopa is typically combined with carbidopa which prevents nausea and premature L-dopa conversion to form a medication to treat symptoms common with PD including automatic movements, difficulty with movements and slowness or stillness. When in the brain, L-dopa is able to convert to dopamine – a neurotransmitter lacking in many individuals with PD and needed to send chemical messages to nerve cells. Generally, L-dopa helps improve the quality of life of PD patients.
Why did they use tomatoes?
L-dopa can be made synthetically (common) and small amounts can be found in a few biological sources such as the seeds of velvet bean (Mucuna prutiens) and in walnuts. The functionality of L-dopa in plants is believed to have defensive properties (repellent to avoid being attacked by predators) and causing detrimental effects on neighbouring species by preventing root growth. The velvet bean, in particular, is not ideal for mass production as it is difficult to harvest due to its stiff hairs that contain mucunain which is an enzyme that causes irritation and due to the presence of tryptamines which cause hallucinations for PD patients.
The idea is that: if we can take easily harvested plants that do not naturally create L-dopa and force them to do so, we can increase the amount of the drug being produced and make it more accessible. Tomatoes naturally have “well-characterized genome[s]”, they have been studied before (tools and analysis techniques are available) and are commonly consumed worldwide (high nutritional value) – making it a good candidate. Additionally, tomatoes have high levels of ascorbate which is beneficial for preventing L-dopa oxidation. Its oxidation forms the intermediate dopaquinone, a precursor to melanin formation which can cause oxidative stress – a process that should be avoided.
What did the study find?
The authors were able to get tomatoes to produce L-dopa at similar levels to the non-seeded foods that naturally accumulate L-dopa. The production was as high as 0.27% dry weight of the fruit. For treatment, a dose of L-dopa is under 500mg/day achievable by consuming around 2 kilograms of fresh L-dopa-tomatoes.
Side benefits included: improved shelf-life, increased longevity of fruit firmness and reduced vulnerability to a strain of fungus (B. cinerea).
What does that mean for PD?
Some patients with PD suffer adverse effects (nausea, behavioural changes, vomiting) from the synthetically made L-dopa, having more biological options for obtaining the drug would be beneficial for those people. It has also been reported that natural L-dopa from velvet bean seeds results in better effects suggesting that obtaining the drug naturally might be more effective. In addition, if L-dopa-tomatoes are mass-produced they could be a more accessible and cost-reducing way to administer the drug to anyone suffering from PD symptoms.
Of course, this study doesn’t come without challenges. Eating 2 kilograms of tomatoes a day would be terrible for anyone (including tomato lovers!). Future experiments would need to improve the yield of L-dopa per tomato, test the effects of tomato-derived L-dopa on brain function and ensure that the process of production is efficient.
Breitel, D., Brett, P., Alseekh, S., Fernie, A. R., Butelli, E., & Martin, C. (2020). Metabolic
engineering of tomato fruit enriched in L-DOPA. Metabolic Engineering.
Gandhi, K. R., & Saadabadi, A. (2019). Levodopa (L-Dopa). In StatPearls [Internet].
Parkinson’s Foundation. Levodopa. [online]. Retrieved on