Innovative Yeast Technology Revolutionizes Macrocyclic Peptide Production

In a groundbreaking study led by researchers at Ca’ Foscari University of Venice, an innovative method has been developed to produce and analyze a wide array of macrocyclic peptides, molecules that are gaining prominence in modern medicine. This research, published in the journal Nature Communications on June 28, 2025, involves collaboration with experts from Japan, China, Switzerland, and Italy, marking a significant advancement in pharmaceutical technology.

Macrocyclic peptides are characterized by their unique structure, which allows for precision targeting of biological pathways, stability, and reduced side effects compared to traditional pharmaceuticals. However, conventional methods for discovering and testing these peptides are often slow, complex, and environmentally taxing. To address these challenges, the research team engineered brewer's yeast cells to function as miniature factories that can produce a variety of macrocyclic peptides.

According to Dr. Sara Linciano, lead author and postdoctoral researcher at Ca’ Foscari’s Department of Molecular Sciences and Nanosystems, “We manipulated yeast cells so that each one functions as a ‘micro-factory’ that becomes fluorescent when producing a specific compound. This allowed us to analyze 100 million different peptides rapidly and effectively.”

The innovative production process employs advanced fluorescence-based techniques, enabling the screening of billions of yeast micro-factories in a matter of hours. This method is not only faster but also more environmentally friendly, addressing the ecological concerns associated with traditional peptide synthesis. Dr. Ylenia Mazzocato, co-leader of the study, emphasized the sustainability aspect: “By exploiting the natural machinery of yeast, we produce peptide molecules that are biocompatible and biodegradable, making them safe for health and the environment—a truly ‘green pharma’ approach.”

To ensure the efficacy of these newly synthesized peptides, the research team conducted structural analysis using X-ray crystallography. Zhanna Romanyuk, a contributor to this aspect of the study, noted, “Using X-ray crystallography, we demonstrated the excellent binding properties of these peptides, confirming their precision and potency.”

This innovative technology could significantly enhance drug discovery, particularly for challenging targets that conventional drugs struggle to address. Alessandro Angelini, associate professor and study coordinator, highlighted the potential for revolutionizing treatments: “We are pushing the boundaries of this technology to create macrocyclic peptides that can deliver advanced therapies directly to specific cells, potentially revolutionizing treatments. This could greatly benefit patient health and have substantial scientific and economic impacts.”

The research aligns with the National Recovery and Resilience Plan (PNRR), supported by the European Union’s Next Generation EU initiative, and involved multidisciplinary collaboration from Ca’ Foscari University of Venice, Kyoto Institute of Technology (KIT), Chinese Academy of Sciences, University of Padova, and École Polytechnique Fédérale de Lausanne (EPFL).

As a testament to its commercial viability, part of this technology has been patented by Ca’ Foscari and acquired by the startup Arzanya S.r.l. Dr. Angelini expressed pride in the recognition of their work: “Seeing our technology gain international recognition makes me proud. I hope Arzanya S.r.l. can provide our talented young researchers with the opportunity to pursue their passions here in Italy, without necessarily needing to move abroad.”

This research not only paves the way for future discoveries in peptide-based therapies but also exemplifies the potential for academic and commercial collaboration in the field of biomedicine, promising a new era of drug development driven by sustainable practices and innovative methodologies.