Science: a major breakthrough! To reveal the complete synthetic pathway of vincristine, a famous anticancer drug

May 16, 2018 / BIOON / - -- since a valuable natural product, vinblastine, was discovered by a Canadian research team in the 1950s, it has been used as an anticancer drug It is a powerful cell division inhibitor, used to treat lymphoma, testicular cancer, breast cancer, bladder cancer and lung cancer It was found in the leaves of the madagasca periwinkle In a new breakthrough study, Professor Sarah O'Connor and his team at John inners center in the UK finally found the last several unknown genes used to synthesize the chemical vinblastine in the genome of Catharanthus roseus after 15 years of research The relevant research results were published online in the journal Science on May 3, 2018, and the paper title is "missing enzymes in the biosynthesis of the anticoncer drug vinblastine in Madagascar periwinkle" Until now, the complex chemical mechanism of vinblastine synthesis from Catharanthus roseus has not been fully understood As a result, it has been laborious to obtain this long-lived chemical - it requires about 500 kg of dried vinblastine leaves to produce 1 g of vinblastine But in the new study, the researchers used modern genomic sequencing techniques to identify the last unknown genes in this pathway The study also identified enzymes used to produce vinblastine precursors, including catharanthine and tabersonine It is easy to couple these enzymes to synthesize vinblastine by using synthetic biological technology Professor O'Connor said, "vinblastine is one of the most complex natural products with medicinal activity in plants, which is why in the past 60 years, so many people have been trying to achieve the results we have achieved in this new research I can't believe that our research was successful in the end With this information, we can now try to increase the content of vinblastine produced in this plant, or introduce synthetic genes into hosts such as yeast or plants to increase its production " Professor O'Connor also pointed out that the new study is based on the work of many other research groups around the world who have been working for many years to elucidate the synthesis pathway of vinblastine Professor O'Connor expects her team or others to be able to produce micrograms of vinblastine or its precursor, vindoline or vinblastine, in the next 12 to 18 months in this highly competitive field In the new study, the researchers used modern sequencing and genomic techniques, as well as traditional chemical methods that relied on intuition and scientific literature dating back to the 1960s and 1970s Overall, they calculated that it took 31 steps to synthesize the final product of vinblastine from a major chemical precursor through a series of reactions One molecule in this series of reactions - its chemical name is dihydroprecondylocarpine acetate - is very volatile (Bio Valley Com) reference: Lorenzo caputi1, Jakob franke1, *, Scott C Farrow et al Missing enzymes in the biosynthesis of the anther drug vinblastine in madagasca periwinkle Science, published online: 03 may 2018, DOI: 10.1126/science.aat4100