Unlocking the Synthetic Potential of Yarrowia lipolytica: Innovating Gene Expression Tools.

Yarrowia lipolytica, with its robust lipid metabolism capabilities, efficient secretion system and generally recognised as safe (GRAS) status, has become a highly promising microbial chassis in synthetic biology. However, compared with model microorganisms such as Saccharomyces cerevisiae, the underdevelopment of gene expression tools in Y. lipolytica has become a critical bottleneck, limiting its industrial application. Currently, its core tools face two critical challenges: promoters with limited dynamic regulatory capacity, leading to metabolic flux imbalance; and gene editing systems plagued by low efficiency and poor multiplex compatibility. This opinion article focuses on these two pivotal directions to dissect their technical bottlenecks and propose innovative solutions: constructing dynamic transcriptional regulatory modules through machine learning guided design and synthetic biology approaches and developing orthogonal CRISPR systems and multiplex editing platforms.