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Engineering Yeast Extracellular Vesicle Biogenesis Through Rewiring Membrane Trafficking Pathways
Yueyan Li1, XiaoRan Ma1, Lichao Zhang1
1School of Life Sciences, Tianjin University, Tianjin, China.
Microbial Biotechnology
|March 28, 2026
Summary
This study enhances understanding of yeast-derived extracellular vesicle (EV) biogenesis using Saccharomyces cerevisiae. Researchers boosted EV production and cargo loading, revealing key protein sorting mechanisms for therapeutic applications.
Area of Science:
- Biotechnology
- Cell Biology
- Microbiology
Background:
- Extracellular vesicles (EVs) show therapeutic potential, but their biogenesis mechanisms are not fully understood.
- Saccharomyces cerevisiae is a safe, well-characterized yeast that naturally produces abundant EVs, making it a suitable model for study.
- Elucidating EV biogenesis in yeast is crucial for harnessing their therapeutic capabilities.
Purpose of the Study:
- To investigate the mechanisms of EV biogenesis and cargo loading in Saccharomyces cerevisiae.
- To establish a tractable model system in S. cerevisiae for studying and engineering EV production.
- To identify proteins involved in yeast-derived extracellular vesicles (YDEVs) biogenesis and cargo selection.
Main Methods:
- Combined multicopy expression of chicken interferon-λ (ChiIFN-λ) with cell wall perturbation to increase EV yield.
- Utilized quantitative proteomics to identify EV-associated proteins.
- Performed functional analyses of key vesicle trafficking proteins (SNARE, ESCRT, Rab) and specific SNARE proteins (Sso2, Nyv1).
Main Results:
- Achieved a tenfold increase in EV yield and efficient ChiIFN-λ incorporation into EVs.
- Identified 1555 EV-associated proteins, including 501 transmembrane proteins from various organelles.
- Demonstrated that ChiIFN-λ overexpression and cell wall stress alter vesicle trafficking regulators, reprogramming intracellular pathways.
- Found Sso2 and Nyv1 SNARE proteins enriched in EV membranes, influencing EV size and subpopulations.
Conclusions:
- Revealed conserved protein-sorting machinery governing yeast-derived extracellular vesicles (YDEVs) biogenesis.
- Established Saccharomyces cerevisiae as a powerful platform for engineered EV production and mechanistic studies.
- The findings provide insights into EV cargo loading and biogenesis for future therapeutic development.
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