Efficient biosynthesis of d‐ribose using a novel co‐feeding strategy in Bacillus subtilis without acid formation

Normally, low d‐ribose production was identified as responsible for plenty of acid formation by Bacillus subtilis due to its carbon overflow. An approach of co‐feeding glucose and sodium citrate is developed here and had been proved to be useful in d‐ribose production. This strategy is critical because it affects the cell concentration, the productivity of d‐ribose and, especially, the formation of by‐products such as acetoin, lactate and acetate. d‐ribose production was increased by 59·6% from 71·06 to 113·41 g l−1 without acid formation by co‐feeding 2·22 g l−1 h−1 glucose and 0·036 g l−1 h−1 sodium citrate to a 60 g l−1 glucose reaction system. Actually, the cell density was also enhanced from 11·51 to 13·84 g l−1. These parameters revealed the importance of optimization and modelling of the d‐ribose production process. Not only could zero acid formation was achieved over a wide range of co‐feeding rate by reducing glycolytic flux drastically but also the cell density and d‐ribose yield were elevated by increasing the hexose monophosphate pathway flux. Significance and Impact of the Study Bacillus subtilis usually produce d‐ribose accompanied by plenty of organic acids when glucose is used as a carbon source, which is considered to be a consequence of mismatched glycolytic and tricarboxylic acid cycle capacities. This is the first study to provide high‐efficiency biosynthesis of d‐ribose without organic acid formation in B. subtilis, which would be lower than the cost of separation and purification. The strain transketolase‐deficient B. subtilis CGMCC 3720 can be potentially applied to the production of d‐ribose in industry. Significance and Impact of the Study: Bacillus subtilis usually produce d‐ribose accompanied by plenty of organic acids when glucose is used as a carbon source, which is considered to be a consequence of mismatched glycolytic and tricarboxylic acid cycle capacities. This is the first study to provide high‐efficiency biosynthesis of d‐ribose without organic acid formation in B. subtilis, which would be lower than the cost of separation and purification. The strain transketolase‐deficient B. subtilis CGMCC 3720 can be potentially applied to the production of d‐ribose in industry.