PMID- 31363033
OWN - NLM
STAT- MEDLINE
DCOM- 20200427
LR  - 20200427
IS  - 2150-7511 (Electronic)
VI  - 10
IP  - 4
DP  - 2019 Jul 30
TI  - Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family 
      Regulator GcdR in Pseudomonas putida KT2440.
LID - 10.1128/mBio.01570-19 [doi]
LID - e01570-19
AB  - Glutarate, a metabolic intermediate in the catabolism of several amino acids and 
      aromatic compounds, can be catabolized through both the glutarate hydroxylation 
      pathway and the glutaryl-coenzyme A (glutaryl-CoA) dehydrogenation pathway in 
      Pseudomonas putida KT2440. The elucidation of the regulatory mechanism could 
      greatly aid in the design of biotechnological alternatives for glutarate 
      production. In this study, it was found that a GntR family protein, CsiR, and a 
      LysR family protein, GcdR, regulate the catabolism of glutarate by repressing the 
      transcription of csiD and lhgO, two key genes in the glutarate hydroxylation 
      pathway, and by activating the transcription of gcdH and gcoT, two key genes in 
      the glutaryl-CoA dehydrogenation pathway, respectively. Our data suggest that 
      CsiR and GcdR are independent and that there is no cross-regulation between the 
      two pathways. l-2-Hydroxyglutarate (l-2-HG), a metabolic intermediate in the 
      glutarate catabolism with various physiological functions, has never been 
      elucidated in terms of its metabolic regulation. Here, we reveal that two 
      molecules, glutarate and l-2-HG, act as effectors of CsiR and that P. putida 
      KT2440 uses CsiR to sense glutarate and l-2-HG and to utilize them effectively. 
      This report broadens our understanding of the bacterial regulatory mechanisms of 
      glutarate and l-2-HG catabolism and may help to identify regulators of l-2-HG 
      catabolism in other species.IMPORTANCE Glutarate is an attractive dicarboxylate 
      with various applications. Clarification of the regulatory mechanism of glutarate 
      catabolism could help to block the glutarate catabolic pathways, thereby 
      improving glutarate production through biotechnological routes. Glutarate is a 
      toxic metabolite in humans, and its accumulation leads to a hereditary metabolic 
      disorder, glutaric aciduria type I. The elucidation of the functions of CsiR and 
      GcdR as regulators that respond to glutarate could help in the design of 
      glutarate biosensors for the rapid detection of glutarate in patients with 
      glutaric aciduria type I. In addition, CsiR was identified as a regulator that 
      also regulates l-2-HG metabolism. The identification of CsiR as a regulator that 
      responds to l-2-HG could help in the discovery and investigation of other 
      regulatory proteins involved in l-2-HG catabolism.
CI  - Copyright (c) 2019 Zhang et al.
FAU - Zhang, Manman
AU  - Zhang M
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Department of Radiobiology, Institute of Radiation Medicine of Chinese Academy of 
      Medical Science & Peking Union Medical College, Tianjin, People's Republic of 
      China.
FAU - Kang, Zhaoqi
AU  - Kang Z
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Guo, Xiaoting
AU  - Guo X
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Guo, Shiting
AU  - Guo S
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Xiao, Dan
AU  - Xiao D
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Liu, Yidong
AU  - Liu Y
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Ma, Cuiqing
AU  - Ma C
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China.
FAU - Gao, Chao
AU  - Gao C
AD  - State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 
      People's Republic of China jieerbu@sdu.edu.cn pingxu@sjtu.edu.cn.
FAU - Xu, Ping
AU  - Xu P
AD  - State Key Laboratory of Microbial Metabolism, Joint International Research 
      Laboratory of Metabolic & Developmental Sciences, and School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of 
      China jieerbu@sdu.edu.cn pingxu@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Acyl Coenzyme A)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Glutarates)
RN  - 0 (Transcription Factors)
RN  - 2889-31-8 (alpha-hydroxyglutarate)
RN  - 3131-84-8 (glutaryl-coenzyme A)
SB  - IM
MH  - Acyl Coenzyme A/metabolism
MH  - Bacterial Proteins/metabolism
MH  - Glutarates/*metabolism
MH  - Pseudomonas putida/*metabolism
MH  - Transcription Factors/metabolism
PMC - PMC6667623
OTO - NOTNLM
OT  - catabolism
OT  - glutarate
OT  - l-2-hydroxyglutarate
OT  - regulatory mechanism
EDAT- 2019/08/01 06:00
MHDA- 2020/04/28 06:00
PMCR- 2019/07/30
CRDT- 2019/08/01 06:00
PHST- 2019/08/01 06:00 [entrez]
PHST- 2019/08/01 06:00 [pubmed]
PHST- 2020/04/28 06:00 [medline]
PHST- 2019/07/30 00:00 [pmc-release]
AID - mBio.01570-19 [pii]
AID - mBio01570-19 [pii]
AID - 10.1128/mBio.01570-19 [doi]
PST - epublish
SO  - mBio. 2019 Jul 30;10(4):e01570-19. doi: 10.1128/mBio.01570-19.