Investigation of mannitol as a potential substrate for production of 2′-fucosyllactose in Yarrowia lipolytica

Mannitol, boasting abundant availability in marine biomass resource, represents a promising feedstock for biomanufacturing. Herein, Yarrowia lipolytica was found to synthesize 2′-fucosyllactose (2′-FL) more efficiently when using mannitol and lactose as substrate, compared to glucose and lactose. Notably, the strain maintained robust growth and 2′-FL production even when cultivated in brown algae processing wastewater. Transcriptome analysis of Y. lipolytica grown on mannitol revealed that two endogenous hexose transporters (Yht1 and Yht3) potentially modulated mannitol uptake. By optimizing the mannitol transporter and the GDP-d-mannose synthesis pathway, a 2′-FL producing strain was constructed with a titer of 9 g/L. Fed-batch fermentation in an inorganic salt medium supplemented with mannitol and lactose elevated the 2′-FL titer to 27.6 g/L. Collectively, this study demonstrates the efficacy of mannitol for 2′-FL biosynthesis and advances the sustainable utilization of algal resources.