Volemitol production from Yarrowia lipolytica via transaldolase gene (TAL) disruption and erythrose-4-phosphate (E4P) flux regulation

Volemitol (D-glycero-D-manno-Heptitol, C₇H₁₆O₇ with CAS No.488–38–0), a seven-carbon (C7) sugar-derived alcohol, has the potential to be used as a natural sweetener. The natural scarcity of sugar alcohols restricts their practical uses. However, Yarrowia lipolytica has shown significant promise in industrial production due to its capability to efficiently produce sugar alcohols like erythritol, D-threitol, mannitol, and xylitol by generating key biosynthetic intermediates through glycolysis and the phosphopentose (PPP) pathway. In this study, the transaldolase gene (TAL) in the erythritol synthesis pathway was knocked out in the erythritol-producing Y. lipolytica strain CGMCC7326 to inhibit erythritol production. TAL-deleted strain Y. lipolytica CGMCC7326ΔTAL exhibited a notable decline in erythritol production; however, a novel substance, volemitol, was generated from glucose at a titer of 50 g/L. Volemitol with 99 % purity was obtained as a white microneedle powder crystal through the enzymatic activity of mannitol dehydrogenase (MDH2), which reduces sedoheptulose to volemitol. The proposed biosynthetic pathway in Y. lipolytica CGMCC7326ΔTAL is: sedoheptulose-7-phosphate was converted to sedoheptulose, then was reduced to volemitol. In conclusion, this study is the first to report efficient volemitol production from glucose via fermentation by engineered Y. lipolytica.