Tomatoes May Offer Novel Cost-effective Source of Levodopa

Tomatoes metabolically engineered to be enriched by the antiparkinsonian drug levodopa may provide a novel, cost-effective source of the drug for patients with Parkinson disease (PD), according to study findings published in Metabolic Engineering.

In management of PD, food-drug interactions are vital to monitor, as factors such as the amount of dietary protein intake can affect the efficacy of levodopa. Moreover, levodopa is naturally produced from tyrosine, an amino acid found in walnuts and other plants, indicating its potential to be administered by natural plant sources.

Scientists from the John Innes Centre in England sought to examine whether levodopa could be synthetically engineered in tomatoes, a fleshy fruit with a complete well-characterized genome that does not normally accumulate the amino acid. Beyond examining the plausibiity of this process, they wanted to see if it may offer opportunities for new phyto-production of levodopa, which over time loses efficacy and can contribute to significant adverse events, particularly motor fluctuations and dyskinesias.

“In this study, L-DOPA-accumulating tomatoes were generated, in a fruit-specific manner, to avoid yield penalties or possible toxicity effects of levodopa on plant development,” explained the study authors. “Tomato fruit were the organ of choice, since they are relatively rich in ascorbate, which could prevent the oxidation of L-DOPA and the generation of melanin, which might, in turn, cause further oxidative stress.”

Researchers inserted a gene encoding a tyrosinase, an enzyme that uses tyrosine to build molecules such as levodopa, that worked to elevate the level of levodopa in the fruit part of the plant. This process then led to higher yields than those associated with levodopa production in the whole plant.

Notably, the levels of levodopa observed in the tomato fruit (150 mg per kg of tomatoes) were comparable to those in other levodopa-accumulating plants. This was achieved without known issues, such as toxicity, that have hindered plant metabolic production of the drug in the past.

Speaking on the potential of these findings and this specific crop, corresponding author of the study Cathie Martin, FRS, project leader, Department of Metabolic Biology, John Innes Centre, said in a statement that because tomatoes can be grown with relatively little infrastructure, production can be scaled up at relatively low cost.

“A local industry could prepare levodopa 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," expanded Martin.

As mentioned in the study’s accompanying press release, PD is a growing issue in developing countries where many residents may not be able to afford the price of synthetic levodopa, indicating the findings’ potential to benefit populations of lower socioeconomic status.

Reference

Breitel D, Brett P, Alseekh S, Fernie AR, Butelli E, Martin C. Metabolic engineering of tomato fruit enriched in L-DOPA. Metab Eng. Published online November 23, 2020. doi:10.1016/j.ymben.2020.11.011