Yeast-Based Platforms for Next-Generation Human Health Applications.

Abstract

Yeast platforms are rapidly transitioning from traditional eukaryotic model organisms to versatile, programmable chassis for next-generation human health applications. This review systematically examines the translational evolution of conventional and non-conventional yeasts including Saccharomyces cerevisiae, Komagataella phaffii, Saccharomyces boulardii, and Yarrowia lipolytica and redefines them as scalable biomanufacturing factories and advanced living therapeutics. We highlight milestone advancements in synthetic biology toolkits that lower technical barriers, such as CRISPR-mediated multiplex editing, modular cloning frameworks, and high-throughput secretion screening. We focus on sophisticated glycoengineering strategies for humanized N-glycosylation, alongside data-driven paradigms that leverage artificial intelligence to predict gene expression and streamline strain design. In clinical domains, we detail the established success of yeast in producing subunit or virus-like particle vaccines (e.g. HBV and HPV) and therapeutic enzymes (e.g. ecallantide), alongside its emerging role as gut-adapted live biotherapeutic products (LBPs) engineered for in situ delivery and biosensing. Finally, we explore specialized non-conventional platforms, focusing on lipid- and acetyl-CoA-rich hosts for lipophilic drug discovery, and stress-tolerant systems optimized for economical, feedstock-flexible bioprocesses. In summary, this review underscores the integrated value of yeast systems across disease modeling, industrial manufacturing, and clinical intervention, charting future directions to address global health challenges.