Chemicals extracted from small flowering plants have been useful in the fight against cancer for decades. After 60 years of searching, scientists have finally revealed how this medically important molecule is made.
Madagascar periwinkle, or rosy periwinkle, is a delightful little plant that adorns many gardens.
But there’s more to this angiosperm than meets the eye, and it can actually save lives.
For decades, scientists have been diligently extracting a chemical called vinblastine from its leaves.
In Canada in the 1950s, scientists discovered vinblastine to be a very useful anti-cancer drug.
It interrupts cell division by stopping cells from entering mitosis and is used against bladder cancer, testicular cancer, lung cancer, ovarian cancer, and breast cancer.
World Health Organization (WHO)
There is one significant problem that reduces the usefulness of vinblastine. That means extraction is extremely difficult and inefficient. Although advances in technology have streamlined the procedure, it remains time-consuming and expensive. Currently, it takes about 500 kilograms of dry leaves to produce just one gram of vinblastine.
Producing this drug requires an incredible amount of effort, so scientists have been on a 60-year mission to understand how plants make this chemical.
The hope is that if they can understand the natural process, they can mimic it in the lab and design a way to produce vinblastine more efficiently and, importantly, at a lower cost.
For the past 15 years, researchers in Professor Sarah O’Connor’s laboratory at the John Innes Center in Norfolk, UK, have been working to understand the genetics of the Madagascar periwinkle.
Finally, Dr. Lorenzo Capti and his team worked with scientists from the Cour d’Avaux Group, based in Tours, France, to solve the final piece of the puzzle.
They used state-of-the-art genome sequencing technology to identify the missing gene in the pathway to vinblastine production.
“Vinblastine is one of the most structurally complex medicinal natural products in plants, which is why so many people have worked hard over the past 60 years to get to where we are in this research. That’s why I did it. I can’t believe we’ve finally come this far. ”
Professor Sarah O’Connor
As the study authors also note, their findings build on years of research conducted in many laboratories around the world. It was truly a collaborative effort.
Their recent paper titled “Deficiency of an enzyme in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle” was published in the journal
Using modern technology, traditional chemistry, and literature written in the 1960s and ’70s, they pieced together the chemical steps needed to convert the precursor molecule to vinblastine. There were a whopping 31 steps in total. Periwinkle is certainly an impressive plant.
The enzymes they identified can be combined using synthetic biology techniques already in use, creating a much-needed shortcut to producing vinblastine.
There’s good reason to be excited about these results. Professor O’Connor said: “With this information, we will be able to increase the amount of vinblastine produced either in plants or by introducing synthetic genes into hosts such as yeast or plants.” Masu.
They predict that within the next 12 to 18 months, their lab or a competitor’s lab should be able to produce small amounts of vinblastine or its precursors vindoline and catharanthine.
