title: Efficient biosynthesis of d-ribose using a novel co-feeding strategy in Bacillus subtilis without acid formation.
abstract: 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-1without acid formation by co-feeding 2·22 g l-1h-1glucose and 0·036 g l-1h-1sodium citrate to a 60 g l-1glucose 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, China.|College of Biotechnology and Pharmaceutical Engineering, National Engineering Technique Research Center for Biotechnology, Nanjing Tech University, Nanjing, China.|Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, China.|College of Biotechnology and Pharmaceutical Engineering, National Engineering Technique Research Center for Biotechnology, Nanjing Tech University, Nanjing, China.|Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Nanjing Tech Law School, Nanjing Tech University, Nanjing, China.
authors.forename: N N
authors.initials: NN
authors.lastname: Li
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, China.|College of Biotechnology and Pharmaceutical Engineering, National Engineering Technique Research Center for Biotechnology, Nanjing Tech University, Nanjing, China.|Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, China.|College of Biotechnology and Pharmaceutical Engineering, National Engineering Technique Research Center for Biotechnology, Nanjing Tech University, Nanjing, China.|Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, Nanjing, China.
authors.forename: H J
authors.initials: HJ
authors.lastname: Ying
mesh_terms: D000093:Acetoin / Q000378:metabolism; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002951:Citrates / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; D012266:Ribose / Q000096:biosynthesis*; D000077559:Sodium Citrate; D014174:Transketolase / Q000172:deficiency / Q000235:genetics
chemical_list: D002951:Citrates; D000077559:Sodium Citrate; D012266:Ribose; D000093:Acetoin; D014174:Transketolase; D005947:Glucose
keywords: 
  Bacillus subtilis
  ; acid formation; carbon overflow; d-ribose; fed-batch; sodium citrate