Engineering the yeast Yarrowia lipolytica for biomanufacturing

The oleaginous yeast Yarrowia lipolytica has become a prominent cell factory for industrial biotechnology due to its robust physiology and metabolic versatility. The genetic toolkits have advanced from early approaches based on nonhomologous end joining to precise CRISPR editing and, recently, to high-throughput genome engineering. Genome-scale metabolic modeling, ‘omic data, and other systems metabolic engineering approaches further accelerate the development of Y. lipolytica strains for biomanufacturing. This review summarizes recent progress in the metabolic engineering of Y. lipolytica, spanning genome editing strategies, systems-level approaches, and representative industrial and biotechnological applications with commercial potential. Together, these advances position Y. lipolytica as a leading microbial workhorse for biomanufacturing. • Y. lipolytica gains recognition in industrial and academic biotechnology. • High-throughput and systems approaches streamline pathway optimization. • Diverse high-titer products highlight strong commercial promise. • Remaining challenges and future directions are critically discussed.