Artificial plant alkaloids could help demystify biosynthesis.

Researchers at the Massachusetts Institute of Technology, in Cambridge, US, have made tailored alkaloids by feeding periwinkle plant cells with tagged versions of their usual starting materials. The tags can be used to purify the resulting alkaloids and potentially to label plant enzymes along the way, allowing a unique insight into alkaloid biosynthesis.

The team studied the synthesis of terpene indole alkaloids, a family of medicinally important compounds that includes the anticancer drugs vincristine and vinblastine. They started with tagged versions of a key intermediate, secologanin, and found that the plant could process it in the same way as natural secologanin, giving tagged alkaloids. The team could then use click chemistry to modify the tags with biotin, and in turn use the biotin to simplify the extraction of alkaloids from the plant.

As well as making it easier to identify and purify new alkaloids, this approach could make it possible to find the enzymes involved in their synthesis. 'We plan to use this tag, along with other modified starting materials that we are currently developing, to attempt to label enzymes involved in the terpene indole alkaloid pathway. Then we could use modern proteomic methods to facilitate the identification of the enzymes,' said team leader Sarah O'Connor.

O'Connor explained that investigating natural product pathways is much more difficult in plants than in bacteria, because plant biochemistry is much more complex. 'Plant biosynthetic enzymes are usually not clustered in one place in the genome. Therefore, each enzyme must be individually isolated and then sequenced and cloned, which is a time consuming, arduous process. New strategies to streamline the identification of plant enzymes are greatly needed,' said O'Connor.

Clare Boothby