Metabolic engineering combined with fermentation optimization enables sustainable production of erythritol by Yarrowia lipolytica from peanut meal and glucose.

Peanut meal (PM) is rich in proteins and fatty acids, which enables it to be a valuable substrate for microbial growth. This study aimed to investigate the effect of PM on the growth and erythritol production of Yarrowia lipolytica CA20 and to establish a procedure for low-cost erythritol production using PM. We found that PM could be used as the only medium component, except for glucose, to support cell growth and erythritol production during submerged fermentation. After optimization of medium compositions and growth conditions, erythritol of 125.25 ± 4.8 g/L was obtained after fermentation for 144 h in a 3.7-L bioreactor, with a yield of 0.69 ± 0.03 g/g. Transcriptome analysis showed that the enhanced erythritol production by CA20 was associated with an increased activity of the metabolism of carbohydrates, amino acids, and lipids. Condition optimization elevated the activity of glucose-6-phosphate dehydrogenase (ZWF1) and phosphogluconate dehydrogenase (GND1) involved in erythritol synthesis. Moreover, hyphal formation of Y. lipolytica was completely inhibited in medium with PM. Besides, A002891 and A001489 were identified to be the key genes associated with erythritol production. Finally, a robust strain, Yarrowia lipolytica CE1, was constructed by deletion of A002891 combined with overexpression of A001489 in CA20, which was able to produce erythritol of 168.78 ± 10 g/L within 108 h from PM and glucose, with a yield of 0.73 ± 0.05 g/g. Collectively, this study provides a valuable way for economical erythritol production and a high-value-added conversion of PM.