Expanding biotechnological applications of Yarrowia lipolytica: Key advances in the past decade

Abstract

Yarrowia lipolytica is a non-conventional yeast with innate oleaginous metabolism and unusual tolerance for hydrophobic substrates, positioning it as a prime chassis for waste-enabled precision fermentation. In this review, we consolidate advances associated with Yarrowia over the past decade into a coherent, trait-centered framework that links biological capabilities to manufacturing performance. We studied genetic toolkits, adaptive laboratory evolution and mating/fusion for strain hardening and phenotype expansion, and combinatorial metabolic engineering strategies (push-pull-block lipid routing, stage- and compartment-specific expression, export engineering) that together improved production titer, rate, and yield across various scales. By organizing metabolic products based on core pathways, namely, the tricarboxylic acid cycle, mevalonate pathway, pentose phosphate pathway, and fatty acid biosynthesis, and pairing each class with the specific chassis edits that enabled leading titers, we provide actionable guidance for target selection and de-risked development. Finally, we propose a roadmap leveraging emerging approaches, AI-guided design, intensified bioprocessing, and precision co-cultures, as key enablers of a scalable, circular bioeconomy with Y. lipolytica as a platform strain.