VENICE – Scientists at Ca’ Foscari University of Venice, collaborating with researchers from Japan, China, Switzerland, and Italy, have pioneered a novel approach for the rapid production and analysis of macrocyclic peptides, increasingly vital molecules in modern medicine. The study, published in Nature Communications, utilizes common brewer’s yeast, transforming billions of these microorganisms into miniature fluorescent factories, each capable of generating unique peptides with potential therapeutic uses.

Macrocyclic peptides hold significant promise as drugs due to thier precision targeting, stability, and safety profiles, often resulting in fewer side effects compared to traditional pharmaceuticals. Though, traditional methods for discovering and testing these peptides are frequently enough complex, difficult to control, slow, and environmentally damaging.

To address these challenges, the research team genetically engineered common brewer’s yeast cells to individually produce diverse macrocyclic peptides. Each yeast cell functions as a tiny factory that emits light when producing the compound,enabling scientists to quickly identify promising peptides. Employing advanced fluorescence-based techniques, the team screened billions of these micro-factories in just a few hours, a process considerably faster and more environmentally friendly than existing methods.

Sara Linciano, lead author and postdoctoral researcher at Ca’ Foscari’s Department of Molecular Sciences and Nanosystems, explains: “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.”

Sustainable and Precise Drug Discovery

“By exploiting the natural machinery of yeast, we produce peptide molecules that are biocompatible and biodegradable, making them safe for health and the habitat, a truly ‘green pharma’ approach.”

Ylenia Mazzocato, co-leader of the study, highlights the sustainability of their approach: “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.”

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

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

This research was conducted as part of the National Recovery and Resilience Plan (PNRR), supported by the European Union’s Next Generation EU initiative.It involved multidisciplinary teams 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),including experts in chemistry,biophysics,biochemistry,and computational sciences.

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