Engineering yeast cell factories to produce anticancer drugs: what a thrilling challenge!
Since ancient times baker’s yeast (Saccharomyces cerevisiae) has been used by human in winemaking, baking, and brewing.
Nowadays, modern tools of molecular biology and genetics have made this yeast a very precious tool that can be used to produce a variety of molecules, such as anti-cancer drugs.
In particular, the tropical plant Madagascar periwinkle (Catharanthus roseus) is naturally able to synthesize anti-cancer monoterpene indole alkaloids (MIA), such as vinblastine and vincristine.
The C. roseus MIA biosynthetic pathway, regarded as the most complex pathway in all living organisms, shows surprising compartmentation at both cellular and subcellular levels. This drastic compartmentation is potentially responsible for the extremely low level of production of MIA in planta.
The present challenge consists in developing recombinant yeast cell factories able to produce, at an industrial scale, vindoline and catharanthine, two precursors of highly valuable anticancer MIA originally produced by C. roseus.
To achieve this ambitious goal, a combined approach using a variety of cutting-edge tools for metabolic engineering and gene editing is required.
Anti-cancer drugs; Monoterpene Indole Alkaloids (MIA); secondary metabolites; traditional medicinal plants; yeast metabolic engineering; bio-reactor.
Dr Grégory Guirimand,
LE STUDIUM Research Fellow / ARD2020 BIOPHARMACEUTICALS Programme