Engineer yeast to produce medicinal monoterpene indole alkaloids

[Release time]:2022-10-02  [Hits]:922

Speaker:Jie Zhang,Senior Research Fellow

Title:“Engineer yeast to produce medicinal monoterpene indole alkaloids”

Time:Oct 5th 2022,15: 00 -16:00pm [Beijing]

Tencent Meeting:https://meeting.tencent.com/dm/42eFz51r56rK

 

Abstract:

Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including anti-cancer, anti-hypertensive, anti-malarial, anti-addiction, analgesic, etc. As MIAs are difficult to chemically synthesize, their supply is exclusively dependent on plant extraction, which is vulnerable to factors such as plant diseases, natural disasters, pandemics and interruptions in global logistics. For example, a shortage of the chemotherapeutics vinblastine and vincristine has interrupted the cancer treatments of many children patients, because no alternative medicines are available. To establish an alternative source of these medicinal alkaloids independent of their natural plant producers, we engineered the baker’s yeast S. cerevisiae to produce strictosidine, a common precursor of all MIAs. We also demonstrate the biosynthesis of vindoline and catharanthine using yeast fermentation, and chemically coupled them to produce the anti-cancer drug vinblastine. In principle, similarly engineered yeast strains could produce more than 3,000 natural MIAs and their unnatural analogues.

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