Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440

ABSTRACT 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 re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Manman Zhang, Zhaoqi Kang, Xiaoting Guo, Shiting Guo, Dan Xiao, Yidong Liu, Cuiqing Ma, Ping Xu, Chao Gao
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	l-2-hydroxyglutarate catabolism glutarate regulatory mechanism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/859c880cd71348b2b576a7b894a35865
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:859c880cd71348b2b576a7b894a35865
record_format	dspace
spelling	oai:doaj.org-article:859c880cd71348b2b576a7b894a358652021-11-15T16:22:09ZRegulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT244010.1128/mBio.01570-192150-7511https://doaj.org/article/859c880cd71348b2b576a7b894a358652019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01570-19https://doaj.org/toc/2150-7511ABSTRACT 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.Manman ZhangZhaoqi KangXiaoting GuoShiting GuoDan XiaoYidong LiuCuiqing MaPing XuChao GaoAmerican Society for Microbiologyarticlel-2-hydroxyglutaratecatabolismglutarateregulatory mechanismMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	l-2-hydroxyglutarate catabolism glutarate regulatory mechanism Microbiology QR1-502
spellingShingle	l-2-hydroxyglutarate catabolism glutarate regulatory mechanism Microbiology QR1-502 Manman Zhang Zhaoqi Kang Xiaoting Guo Shiting Guo Dan Xiao Yidong Liu Cuiqing Ma Ping Xu Chao Gao Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
description	ABSTRACT 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.
format	article
author	Manman Zhang Zhaoqi Kang Xiaoting Guo Shiting Guo Dan Xiao Yidong Liu Cuiqing Ma Ping Xu Chao Gao
author_facet	Manman Zhang Zhaoqi Kang Xiaoting Guo Shiting Guo Dan Xiao Yidong Liu Cuiqing Ma Ping Xu Chao Gao
author_sort	Manman Zhang
title	Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
title_short	Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
title_full	Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
title_fullStr	Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
title_full_unstemmed	Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440
title_sort	regulation of glutarate catabolism by gntr family regulator csir and lysr family regulator gcdr in <named-content content-type="genus-species">pseudomonas putida</named-content> kt2440
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/859c880cd71348b2b576a7b894a35865
work_keys_str_mv	AT manmanzhang regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT zhaoqikang regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT xiaotingguo regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT shitingguo regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT danxiao regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT yidongliu regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT cuiqingma regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT pingxu regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440 AT chaogao regulationofglutaratecatabolismbygntrfamilyregulatorcsirandlysrfamilyregulatorgcdrinnamedcontentcontenttypegenusspeciespseudomonasputidanamedcontentkt2440
_version_	1718426912241483776

Regulation of Glutarate Catabolism by GntR Family Regulator CsiR and LysR Family Regulator GcdR in <named-content content-type="genus-species">Pseudomonas putida</named-content> KT2440

Ejemplares similares