Zhejiang University researchers boost cancer drug precursor production in yeast by 1,000 times

A research team at Zhejiang University has cracked a molecular puzzle, turning ordinary yeast into a powerful factory for an expensive cancer drug and boosting its production by a thousand times.

The anticancer drug vinblastine has long been sourced exclusively from the Madagascar periwinkle plant. But it takes 2 tonnes of dried leaves to yield just 1 gram of vinblastine, making it more expensive than gold by weight. This extreme scarcity has kept the drug costly and its supply unreliable for decades.

After years of work, a team led by Zhejiang University professor Lian Jiazhang, in collaboration with Qu Yang’s research group at the University of New Brunswick in Canada and Wang Yajie’s team at Westlake University, broke the deadlock.

They engineered brewer’s yeast to produce 164.9 milligrams per litre (0.022 ounces per gallon) of catharanthine – the direct precursor to vinblastine – inside a fermenter. That is nearly 1,000 times higher than any previously published global figure.

The findings were published by the peer-reviewed journal Science and published as a first release version on July 16.

The foundation for this breakthrough dates back to 2022, when Lian’s team first inserted the 30-step synthesis pathway for vinblastine into yeast. But for a long time, output stayed at just micrograms per litre, far below what would be useful for industry.

In a video from the ZJU-Hangzhou Global Scientific and Technological Innovation Centre, Lian explained the problem: “It came down to the cell’s internal structure. One intermediate in the vinblastine pathway is highly unstable”.