Study Opens Up Madagascar Plant’s Cancer-fighting Potential
Naturally produced by plants, vincamine, vinblastine and vincristine are very important clinic alkaloids used in a variety of treatment strategies including cancer.
Vinblascine and vincristine are derived from the Madagascar periwinkle Catharanthus roseus and are regularly used in the chemotherapy of hematological malignancies such as lymphomas and leukemias.
In spite of its therapeutic importance, the plant’s complex chemical mechanisms to produce these alkaloids in not fully understood. Consequently, access to its life-extending chemistry is not any less complex – approximately 500 kg of dried leaves are required to produce 1g of vinblastine.
Now, scientists at the at the John Innes Centre, after a 15-year long investigation have, finally been able to point to the last missing genes in the genome of the periwinkle that are believed to be exclusively devoted to building these chemicals.
Their work identifies a particular enzyme shown to be dedicated to building vinblastine precursor chemicals, including catharanthine and tabersonine; which can be readily chemically coupled using synthetic biology techniques to give vinblastine.
“Vinblastine is one of the of the most structurally complex medicinally active natural products in plants – which is why so many people in the last 60 years have been trying to get where we have got to in this study. I cannot believe we are finally here,” said Professor O’Connor.
“With this information we can now try to increase the amount of vinblastine produced either in the plant, or by placing synthetic genes into hosts such as yeast or plants.”
The team suspected that the missing enzymes helped transform a single compound into structures that form the frameworks for catharanthine and tabersonine to make vinblastine.
They then searched a database of the periwinkle RNA and identified them and discovered that they were both made at the same time as the plant is producing other enzymes involved in vinblastine synthesis.
In total, the researchers enumerated 31 steps in the chemical chain from the primary chemical precursor to the final product, the alkaloid vinblastine. One molecule in the chain so found to be very volatile because of which the team came to name it the “angry-line” instead of its true scientific name dihydroprecondylocarpine acetate.