The supply of a plant-derived anti-cancer drug can finally meet global demand after a team of scientists from Denmark and the U.S. engineered yeast to produce the precursor molecules, which could previously only be obtained in trace concentrations in the native plant. A study describing the breakthrough was recently published in Nature. The international team included four researchers from the Biological Systems and Engineering Division: Leanne Jade G. Chan, Edward Baidoo, Christopher J. Petzold, and Jay D. Keasling.
“The yeast platform we developed will allow environmentally friendly and affordable production of vinblastine and the more than 3,000 other molecules that are in this family of natural products,” said project co-leader Jay Keasling, who also serves as a scientific director at the Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain), the CEO of the Joint BioEnergy Institute (JBEI), and is a professor of Chemical & Biomolecular Engineering at UC Berkeley. “In addition to vinblastine, this platform will enable production of anti-addiction and anti-malarial therapies as well as treatments for many other diseases.” Keasling is a biochemical engineer who helped launch the now-booming field of synthetic biology when his team successfully transferred the genetic pathway to produce an antimalarial drug, artemisinin, from an herb called sweet wormwood to the laboratory workhorse microbe, E. coli.
Vinblastine and another chemotherapy agent, vincristine, are both natural products of a pink-flowered plant called the Madagascar periwinkle. Their anti-cancer properties were first discovered in the 1950s, and in the decades since, they have become essential medicines. Vinblastine, which inhibits cell division, is used alongside other chemotherapy agents to treat multiple types of cancer, including lymphomas, testicular, ovarian, breast, bladder, and lung cancers. Vincristine inhibits white blood cell production and is a mainstay treatment for childhood lymphoblastic leukemia and non-Hodgkin lymphomas.
Vinblastine and vincristine belong to a group of botanical compounds called monoterpenoid indole alkaloids (MIAs) that have many useful medical applications. Unfortunately, this group is characterized by complicated atomic structures that are often impossible to replicate through synthetic chemistry. So, much like the production of artemisinin before Keasling’s breakthrough, making vinblastine and vincristine requires growing and harvesting huge quantities of the native plant to extract precursor molecules. It takes 500 and 2,000 kilograms of dried Madagascar periwinkle leaves to produce one gram of vinblastine and vincristine, respectively.
Read more at the Berkeley Lab News Center.