Multi-omics guided engineering of a low-foaming Yarrowia lipolytica for sustainable erythritol production from lignocellulosic hydrolysates

Abstract

Erythritol, as an important zero-calorie sweetener, is widely used in food, pharmaceutical, and daily chemical industries. However, its industrial production has long faced two major challenges: high raw material costs and severe foaming during fermentation, which significantly complicate process control and increase operational costs. To address these issues, this study screened a natural low-foaming erythritol-producing strain, Yarrowia lipolytica 167, and demonstrated its capacity for efficient erythritol synthesis using low-cost lignocellulosic biomass as a feedstock. We established an efficient genetic manipulation platform that enabled consecutive rounds of gene editing in this wild-type strain. Through integrated genomic resequencing, comparative transcriptomic, and metabolomic analyses, we systematically elucidated the key metabolic bottlenecks in the erythritol biosynthesis pathway of strain 167. Based on the mechanistic insights provided by multi-omics analysis, precise metabolic engineering of strain 167 was performed, resulting in a 2.3-fold increase in erythritol titer. Subsequently, using wheat straw-derived lignocellulosic hydrolysate as an alternative carbon source in fed-batch fermentation in a 5 L bioreactor, the engineered strain achieved an erythritol titer, yield, and productivity of 214.2 g/L, 0.60 g/g, and 2.23 g/L/h, respectively. This represents the highest production level reported to date for erythritol production from lignocellulosic hydrolysate by Y . lipolytica . This study not only provides a low-foaming engineered strain suitable for the value-added utilization of lignocellulosic resources but also establishes a transferrable research paradigm encompassing superior strain screening, genetic tool development, multi-omics-driven metabolic engineering, and renewable feedstock application.