Advancing transcriptional regulation in Yarrowia lipolytica : from endogenous promoter discovery to synthetic promoter engineering

As an unconventional yeast, Yarrowia lipolytica is increasingly used in biomanufacturing high-value chemicals, including organic acids, sugar alcohols, fatty acid derivatives, and terpenes, owing to its unique physiological and biochemical properties. However, fine-tuning its biosynthetic pathways requires advanced transcriptional regulatory tools, with promoters being the most essential component. Numerous studies have sought to characterize promoter sequences by breaking them into distinct functional elements, while also constructing stronger and inducible synthetic promoters through rational design, modification, and optimization. This review summarizes the progress in discovering endogenous and engineering synthetic promoters in Y. lipolytica. We highlight emerging strategies such as hybrid promoter engineering, core promoter engineering, and transcription factor-based promoter engineering, which expand the promoter toolbox with enhanced properties. Finally, we address the current state of research and identify potential future directions in this field.