Improving riboflavin production by modifying related metabolic pathways in Bacillus subtilis

Riboflavin is a feed additive, food additive and clinical drug, with a significant annual demand of nearly 8000 t. Fermentation using recombinant Bacillus subtilis is currently one of the most important industrial production method for riboflavin. First, a suitable medium was selected and the expression of the ureABC operon was modified. The ykgB gene was overexpressed in B. subtilis RX10, the production of the derivative strain RX20 was increased to 4·61 g l^-1 riboflavin, and the yield was increased to 52 mg riboflavin g^-1 glucose. The relative transcription level of pyr operon in RX20 was reduced to 71%, the production of the derivative strain RX21 was increased to 5·82 g l^-1 riboflavin, and the yield was 76 mg riboflavin g^-1 glucose. The start codon of the pyrE gene in RX21 was modified to 'TTG', the production of the derivative strain RX22 was increased to 7·01 g l^-1 riboflavin, and the yield was 89 mg riboflavin g^-1 glucose. These results indicated that overexpression of the ykgB gene and reduction of the metabolic flux of de novo synthesis of pyrimidine nucleotides were beneficial to the synthesis of riboflavin.