PMID- 34395408
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210817
IS  - 2296-4185 (Print)
IS  - 2296-4185 (Electronic)
IS  - 2296-4185 (Linking)
VI  - 9
DP  - 2021
TI  - Improving the Production of Riboflavin by Introducing a Mutant Ribulose 
      5-Phosphate 3-Epimerase Gene in Bacillus subtilis.
PG  - 704650
LID - 10.3389/fbioe.2021.704650 [doi]
LID - 704650
AB  - Ribulose 5-phosphate (Ru5P) and guanosine 5'-triphosphate (GTP) are two key 
      precursors of riboflavin, whereby Ru5P is also a precursor of GTP. Ribulose 
      5-phosphate 3-epimerase (Rpe) catalyzes the conversion of ribulose 5-phosphate 
      into xylulose 5-phosphate. Inactivation of Rpe can reduce the consumption of 
      Ru5P, enhancing the carbon flux toward riboflavin biosynthesis. Here we 
      investigated the effect of mutation of rpe and other related genes on riboflavin 
      production, physiological and metabolic phenotypes in Bacillus subtilis LY 
      (BSLY). Introducing single nucleotide deletion (generated BSR) or nonsense 
      mutation (generated BSRN) on the genomic copy of rpe, resulting in more than 
      fivefold increase of riboflavin production over the parental strain. BSR process 
      62% Rpe activity, while BSRN lost the entire Rpe activity and had a growth defect 
      compared with the parent strain. BSR and BSRN exhibited increases of the inosine 
      and guanine titers, in addition, BSRN exhibited an increase of inosine 
      5'-monophosphate titer in fermentation. The transcription levels of most 
      oxidative pentose phosphate pathway and purine synthesis genes were unchanged in 
      BSR, except for the levels of zwf and ndk, which were higher than in BSLY. The 
      production of riboflavin was increased to 479.90 +/- 33.21 mg/L when ribA was 
      overexpressed in BSR. The overexpression of zwf, gntZ, prs, and purF also 
      enhanced the riboflavin production. Finally, overexpression of the rib operon by 
      the pMX45 plasmid and mutant gnd by pHP03 plasmid in BSR led to a 3.05-fold 
      increase of the riboflavin production (977.29 +/- 63.44 mg/L), showing the 
      potential for further engineering of this strain.
CI  - Copyright (c) 2021 Yang, Sun, Fu, Xia, Su, Liu, Zhang and Zhang.
FAU - Yang, Bin
AU  - Yang B
AD  - School of Biological Engineering, Dalian Polytechnic University, Dalian, China.
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
FAU - Sun, Yiwen
AU  - Sun Y
AD  - School of Biological Engineering, Dalian Polytechnic University, Dalian, China.
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
FAU - Fu, Shouying
AU  - Fu S
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 
      China.
FAU - Xia, Miaomiao
AU  - Xia M
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
FAU - Su, Yuan
AU  - Su Y
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 
      China.
FAU - Liu, Chuan
AU  - Liu C
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhang, Chunzhi
AU  - Zhang C
AD  - School of Biological Engineering, Dalian Polytechnic University, Dalian, China.
FAU - Zhang, Dawei
AU  - Zhang D
AD  - Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, 
      Tianjin, China.
AD  - University of Chinese Academy of Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20210729
PL  - Switzerland
TA  - Front Bioeng Biotechnol
JT  - Frontiers in bioengineering and biotechnology
JID - 101632513
PMC - PMC8359813
OTO - NOTNLM
OT  - Bacillus subtilis
OT  - pentose phosphate pathway
OT  - riboflavin
OT  - ribulose 5-phosphate 3-epimerase
OT  - truncated protein
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/17 06:00
MHDA- 2021/08/17 06:01
PMCR- 2021/01/01
CRDT- 2021/08/16 06:02
PHST- 2021/05/03 00:00 [received]
PHST- 2021/05/25 00:00 [accepted]
PHST- 2021/08/16 06:02 [entrez]
PHST- 2021/08/17 06:00 [pubmed]
PHST- 2021/08/17 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fbioe.2021.704650 [doi]
PST - epublish
SO  - Front Bioeng Biotechnol. 2021 Jul 29;9:704650. doi: 10.3389/fbioe.2021.704650. 
      eCollection 2021.