New breakthrough in Nature: Anticancer drugs can be synthesized with reprogrammed yeast!

During the summer and fall of 2019, treatment for some cancer patients was interrupted

There are no alternatives to these drugs, isolated from the leaves of Madagascar periwinkle (Catharanthus roseus)

Although periwinkle flowers are common, more than 2,000 kilograms of dried leaves are required to produce 1 gram of vinblastine

An interdisciplinary international team of scientists led by DTU researchers has genetically engineered yeast to produce vindoline and catharanthine

This research could lead to new sources of vindoline, catharanthine and other alkaloids that are completely independent of crop-growing factors such as plant diseases and natural disasters

"We've seen several instances of shortages of these drugs on the market over the past few years

Possible new supply chain for cancer drugs

In addition to demonstrating for the first time an entirely new supply chain for these essential cancer-fighting drugs, the study also demonstrates the longest biosynthetic pathway (or "pipeline") inserted into a microbial cell factory

Vinblastine belongs to the so-called monoterpene indole alkaloids, or MIAs for short

"To demonstrate the feasibility of microbes making all MIAs, we chose one of the most complex chemicals known in phytochemistry

Michael Krogh Jensen, a senior researcher at DTU and one of the study's corresponding authors, added:

"We have to have the right 'people' on the line

The team made 56 gene edits to program the 31-step biosynthetic pathway into baker's yeast

"In this project, we are finding new ways to make complex chemicals that are critical to human health, although the technology may also be useful in agriculture and materials science

According to the authors, among the many new essential MIAs that may be produced based on their new platform are the chemotherapy drugs vincristine, irinotecan and topotecan

Yeast cells hold promise in drug production

The study further highlights recent developments in synthetic biology, where engineered yeast are used for drug production

The production of plant-derived drugs in industrial-scale fermenters using inexpensive and renewable substrates could potentially alleviate future shortages and create a more sustainable economy that does not rely on farmed or rare organisms

Corresponding author Jay D.

"The metabolic pathway we constructed in yeast is the longest biosynthetic pathway ever reorganized in a microorganism
.
This work shows that very long and complex metabolic pathways can be derived from almost any organism and recombinant yeast to provide much needed The treatment, too complex, is synthesized using synthetic chemistry
.
Because yeast itself is scalable, this engineered yeast could one day deliver vinblastine as well as 3,000 other related molecules in this family of natural products
.
Not only will this increase consumer supply, reducing the cost of these products, and production is also environmentally friendly because it does not require harvesting sometimes-rare plants from sensitive ecosystems to obtain molecules
.
"

Original title:

A microbial supply chain for production of the anti-cancer drug vinblastine