Plant scientists at UK’s John Innes Centre unraveled the complex chemistry
of Madagascar periwinkle that opens up the potential for rapid synthesis of cancer-fighting compounds.
In a study in the journal Science, the researchers led by Sarah O’Connor, identified the last missing genes in the genome of the periwinkle that are devoted to building the chemical vinblastine after 15 years of research.
This valuable natural product has been used as an anti-cancer drug since it was discovered in the 1950s.
Found in the leaves of Madagascar periwinkle (Catharanthus roseus), it proved to be a potent inhibitor of cell division and used against lymphomas and testicular, breast, bladder and lung cancers.
However, access to its life-extending chemistry has been labourious. It takes approximately 500 kg of dried leaves to produce 1g of vinblastine.
O’Connor’s team used modern genome sequencing techniques to identify enzymes that build vinblastine precursor chemicals, which include catharanthine and tabersonine.
According to the researchers, these can be readily chemically coupled using synthetic biology techniques to give vinblastine.
“Vinblastine is one of of the most structurally complex medicinally active natural products in plants,” said 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.”
Having assembled the genetic pathway and the chemical structures, the team are now in a position to use the information to create more compounds much more quickly using synthetic biology techniques.
O’Connor anticipated that her group or another in this competitive field would be able to produce microgramme quantities of vinblastine or its precursors, namely vindoline or catharanthine, in the next 12 to 18 months.
