Metabolic Engineering of Kluyveromyces marxianus for Succinic Acid Production

Abstract:

[Objective] This study constructed a succinic acid-producing cell factory for the efficient biosynthesis of succinic acid. [Method] Using Kluyveromyces marxianus (K. marxianus) as the chassis strain, an engineered yeast strain for the biosynthesis of succinic acid through comprehensive metabolic engineering strategies was constructed. These strategies encompassed the disruption of by-product synthesis pathways, enhancement of glycolytic flux, introduction of a heterologous succinic acid biosynthetic pathway, optimization of key enzyme expression, and augmentation of transmembrane transport of succinic acid. Finally, a fermentation process optimization was performed to improve the production performance. [Result] The engineered strain K. marxianus SA011 achieved a succinic acid titer of 10.06 g/L, a yield of 11.4%, and a productivity of 0.14 g/(L·h) in a 5 L bioreactor. [Conclusion] This study provides new insights into the metabolic engineering of K. marxianus and establishes a foundation for the efficient biosynthesis of succinic acid by yeast, facilitating its industrial application.