Random mutagenesis and transcriptomics-guided rational engineering in Zygosaccharomyces rouxii for elevating D-arabitol biosynthesis.

D-arabitol, a versatile compound with applications in food, pharmaceutical, and biochemical industries, faces challenges in biomanufacturing due to poor chassis performance and unclear synthesis mechanisms. This study aimed to enhance the performance of Zygosaccharomyces rouxii to improve D-arabitol production. Firstly, a mutant strain Z. rouxii M075 obtained via atmospheric and room temperature plasma-mediated mutagenesis yielded 42.0 g/L of D-arabitol at 96 h, with about 50 % increase. Transcriptome-guided metabolic engineering of pathway key enzymes co-expression produced strain ZR-M3, reaching 48.9 g/L D-arabitol after 96 h fermentation. Finally, under optimized conditions, fed-batch fermentation of ZR-M3 in a 5 L bioreactor yielded an impressive D-arabitol titer of 152.8 g/L at 192 h, with a productivity of 0.8 g/L/h. This study highlights promising advancements in enhancing D-arabitol production, offering potential for more efficient biomanufacturing processes and wider industrial applications.