From brewery to pharmaceuticals: yeast transforms into a “factory” for compounds

A team of scientists from Ca’ Foscari University of Venice, in collaboration with researchers from Japan, China, Switzerland and Italy, has developed an innovative method to quickly produce and analyse a wide range of macrocyclic peptides — molecules increasingly used in modern medicine. The research, published in Nature Communications, utilises common brewer’s yeast, transforming billions of these microorganisms into tiny fluorescent factories, each capable of producing a unique peptide with potential therapeutic applications.

Macrocyclic peptides are a promising class of drugs because they combine precision, stability and safety, offering fewer side effects than traditional medicines. However, classical methods for discovering and testing them are complex, difficult to control, slow and less environmentally friendly. To overcome these limitations, the research team engineered yeast cells so that each one could individually produce different macrocyclic peptides.

Each yeast cell functions as a tiny factory that becomes fluorescent when it produces the compound, enabling researchers to quickly identify the most promising peptides. Using advanced microfluidics and fluorescence techniques, the team analysed billions of these micro-factories in just a few hours — a process that is considerably faster and more sustainable than current methods.

Sara Linciano, first author of the study and postdoctoral researcher at Ca’ Foscari’s Department of Molecular Sciences and Nanosystems, explains: “We modified yeast cells so that each functions as a ‘micro-factory’ which becomes fluorescent when it produces a specific compound. This allowed us to analyse quickly and efficiently around 100 million different peptides.”

Ylenia Mazzocato, co-lead of the study, highlights the sustainability of the approach: “By harnessing yeast’s natural system, we produce biocompatible and biodegradable peptide molecules, making them safe for both human health and the environment — a true example of green pharma.”

The team also clarified how these peptides bind precisely to their targets. Zhanna Romanyuk, who contributed to the structural analysis, notes: “Using X-ray crystallography, we demonstrated the excellent binding capacity of these peptides, confirming their precision and potency.”

This new method marks a major advance in drug discovery, especially for targets that are difficult to treat with conventional medicines. Alessandro Angelini, Associate Professor and coordinator of the study, emphasises: “We are further developing this technology to produce macrocyclic peptides capable of delivering advanced therapies directly to targeted cells, with the potential to transform treatments. This could provide significant health benefits for patients along with major scientific and economic advantages.”

The study was carried out as part of Italy’s National Recovery and Resilience Plan (PNRR), with support from the European Union’s Next Generation EU initiative, and involved multidisciplinary teams from Ca’ Foscari University of Venice, Kyoto Institute of Technology (KIT), Chinese Academy of Sciences, University of Padua, and École Polytechnique Fédérale de Lausanne (EPFL) — including experts in chemistry, biophysics, biochemistry and computational science.

Part of this technology has already been patented by Ca’ Foscari and recently acquired by the startup Arzanya S.r.l. “Seeing our technology gain international recognition makes me proud,” concludes Angelini. “I hope Arzanya S.r.l. can offer our talented young researchers the opportunity to continue pursuing their passions here in Italy, without necessarily having to move abroad.”