Enhancement of Riboflavin Production by an Enhanced Purine Salvage Pathway in Bacillus subtilis

Recombinant Bacillus subtilis is currently used as a producer for riboflavin biosynthesis. In this study, a novel metabolic engineering strategy for the enhancement of purine salvage pathway in B. subtilis effectively improved the riboflavin biosynthesis by increasing the supply of precursors via an energy-saving route. Mutant strains overexpressing the related genes of salvage pathway exhibited higher production compared to the original strain. Specifically, the deoD-hprT co-overexpressing mutant BR-08 demonstrated a significant increase in riboflavin production, from 1049.84 to 1252.34 mg/L, representing a 19.29% improvement. To further amplify the impact of the salvage pathway, xylose was introduced into the fermentation process as an inducer to upregulate the expression of the relevant genes, while guanosine was added as a direct precursor. Following the optimization of the fermentation conditions, the riboflavin titer of mutant BR-08 reached 1898.58 mg/L. These findings substantiate the efficacy of the purine salvage pathway in enhancing riboflavin biosynthesis and offer a novel strategy for improving biosynthetic efficiency through an energy-conserving mechanism.