PMID- 10919325
OWN - NLM
STAT- MEDLINE
DCOM- 20001124
LR  - 20190915
IS  - 0175-7598 (Print)
IS  - 0175-7598 (Linking)
VI  - 53
IP  - 6
DP  - 2000 Jun
TI  - Production of riboflavin by metabolically engineered Corynebacterium 
      ammoniagenes.
PG  - 674-9
AB  - Improved strains for the production of riboflavin (vitamin B2) were constructed 
      through metabolic engineering using recombinant DNA techniques in Corynebacterium 
      ammoniagenes. A C. ammoniagenes strain harboring a plasmid containing its 
      riboflavin biosynthetic genes accumulated 17-fold as much riboflavin as the host 
      strain. In order to increase the expression of the biosynthetic genes, we 
      isolated DNA fragments that had promoter activities in C. ammoniagenes. When the 
      DNA fragment (P54-6) showing the strongest promoter activity in minimum medium 
      was introduced into the upstream region of the riboflavin biosynthetic genes, the 
      accumulation of riboflavin was 3-fold elevated. In that strain, the activity of 
      guanosine 5'-triphosphate (GTP) cyclohydrolase II, the first enzyme in riboflavin 
      biosynthesis, was 2.4-fold elevated whereas that of riboflavin synthase, the last 
      enzyme in the biosynthesis, was 44.1-fold elevated. Changing the sequence 
      containing the putative ribosome-binding sequence of 3,4-dihydroxy-2-butanone 
      4-phosphate synthase/GTP cyclohydrolase II gene led to higher GTP cyclohydrolase 
      II activity and strong enhancement of riboflavin production. Throughout the 
      strain improvement, the activity of GTP cyclohydrolase II correlated with the 
      productivity of riboflavin. In the highest producer strain, riboflavin was 
      produced at the level of 15.3 g l(-1) for 72 h in a 5-l jar fermentor without any 
      end product inhibition.
FAU - Koizumi, S
AU  - Koizumi S
AD  - Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Machida, Japan. 
      skoizumi@kyowa.co.jp
FAU - Yonetani, Y
AU  - Yonetani Y
FAU - Maruyama, A
AU  - Maruyama A
FAU - Teshiba, S
AU  - Teshiba S
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Appl Microbiol Biotechnol
JT  - Applied microbiology and biotechnology
JID - 8406612
RN  - EC 2.5.1.9 (Riboflavin Synthase)
RN  - EC 3.5.4.16 (GTP Cyclohydrolase)
RN  - EC 5.4.- (Intramolecular Transferases)
RN  - EC 5.4.- (L-3,4-dihydroxy-2-butanone-4-phosphate synthase)
RN  - TLM2976OFR (Riboflavin)
SB  - IM
MH  - Base Sequence
MH  - Corynebacterium/*genetics/metabolism
MH  - GTP Cyclohydrolase/genetics
MH  - *Genetic Engineering
MH  - Industrial Microbiology/methods
MH  - Intramolecular Transferases/genetics
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Riboflavin/*biosynthesis
MH  - Riboflavin Synthase/genetics
EDAT- 2000/08/05 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/05 11:00
PHST- 2000/08/05 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/05 11:00 [entrez]
AID - 10.1007/s002539900295 [doi]
PST - ppublish
SO  - Appl Microbiol Biotechnol. 2000 Jun;53(6):674-9. doi: 10.1007/s002539900295.