An ornamental plant commonly found in India and elsewhere may emerge as the source of one of the largest-selling anti-cancer drugs, vinblastine, with a team of researchers from the UK helping find missing genes involved in the biosynthesis of the chemical.
Sixty years ago, two Canadian scientists studying the anti-diabetic properties of the Madagascar periwinkle, known as nithyakalyani in Tamil and sadabahar in Hindi, stumbled upon its anti-cancer properties. This led to the discovery of vinblastine and vincristine, used to treat various cancers.
Since then, many scientific groups have worked tirelessly to unravel the cellular mechanisms involved in the production of these valuable chemical compounds. They met with only partial success, as many enzymes involved in their biosynthesis were still missing. The complex chemical mechanisms that the plant uses to produce vinblastine remained a puzzle for nearly six decades.
Now, a research team led by Sarah O’Connor, biological chemist at John Innes Centre (JIC) in Norwich, UK, has identified the missing steps in the biosynthesis of vinblastine, opening up a potential avenue for rapid synthesis of the compound.
“Vinblastine is one of the of the most structurally complex medicinally active natural products in plants…which is why so many people in the past 60 years have been trying to get where we have got to in this study. I cannot believe we are finally here,” said O’Connor in a statement.
The JIC scientist, who has been working on the periwinkle plant for over 15 years, is hopeful they can now try to increase the amount of vinblastine produced — either in the plant itself, or by placing synthetic genes in hosts such as yeast or other plants. Scientists from François Rabelais University, Tours, France, also participated in the study.
Producing 1 gram of vinblastine requires about 500 kg of dried periwinkle leaves, so the drug is currently synthesised chemically. The reconstitution of vinblastine biosynthesis, following the discovery of the ‘missing steps’, could provide an additional source of this valuable drug. It is currently used in the treatment of cancers of the lymphomas and bladder, breast and lung.
The scientists, whose work appeared recently in Science journal, were able to identify the final missing genes in the vinblastine pathway. Altogether, 31 steps are involved in the production of vinblastine in the periwinkle plant, whose attractive white-and-pink flowers make it a garden favourite worldwide.
O’Çonnor noted that over the decades, a number of research groups around the world had contributed to the elucidation of the pathway.
The scientists are now eyeing the production of microgram quantities of the drug, establishing the viability of the biosynthesis as a mode of producing commercial vinblastine.