Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.32 (
phosphoenolpyruvate carboxykinase
)
4,204
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nitrosative stress is an ongoing challenge that most organisms have to contend with. When nitric oxide (NO) that may be generated either exogenously or endogenously encounters reactive oxygen species (ROS), it produces a set of toxic moieties referred to as reactive nitrogen species (RNS). As these RNS can severely damage essential biomolecules, numerous organisms have evolved elaborate detoxification strategies to nullify RNS. However, the contribution of cellular metabolism in fending off nitrosative stress is poorly understood. Using a variety of functional proteomic and metabolomic analyses, we have identified how the soil microbe Pseudomonas fluorescens reprogrammed its metabolic networks to survive in an environment enriched by sodium nitroprusside (SNP), a generator of nitrosative stress. To combat the RNS-induced ineffective aconitase (ACN) and tricarboxylic acid (TCA) cycle, the microbe invoked the participation of citrate lyase (CL),
phosphoenolpyruvate carboxylase
(
PEPC
) and pyruvate phosphate dikinase (PPDK) to convert citrate, the sole source of carbon into pyruvate and ATP. These enzymes were not evident in the control conditions. This metabolic shift was coupled to the concomitant increase in the activities of such classical RNS detoxifiers as nitrate reductase (NR), nitrite reductase (NIR) and S-nitrosoglutathione reductase (
GSNOR
). Hence, metabolism may hold the clues to the survival of organisms subjected to nitrosative stress and may provide therapeutic cues against RNS-resistant microbes.
...
PMID:The metabolic reprogramming evoked by nitrosative stress triggers the anaerobic utilization of citrate in Pseudomonas fluorescens. 2214 48
The mycobacteria comprise both pathogenic and nonpathogenic bacteria. Although several features related to pathogenicity in various mycobacterial species, such as
Mycobacterium tuberculosis
, have been studied in great detail, methylotrophy, i.e., the ability of an organism to utilize single-carbon (C
1
) compounds as the sole source of carbon and energy, has remained largely unexplored in mycobacteria. Reports are available that suggest that mycobacteria, including
M. tuberculosis
and
M. smegmatis
, are capable of utilizing alternative C
1
compounds to meet their carbon and energy requirements. However, physiological pathways that are functional in mycobacteria to utilize such carbon compounds are only poorly understood. Here we report the identification and characterization of the gene products required for establishing methylotrophy in
M. smegmatis
We present
N
,
N
-dimethyl-
p
-nitrosoaniline (NDMA)-dependent methanol oxidase (Mno) as the key enzyme that is essential for the growth of
M. smegmatis
on methanol. We show that Mno has both methanol and
formaldehyde dehydrogenase
activities
in vitro
Further,
M. smegmatis
is able to utilize methanol even in the absence of the major
formaldehyde dehydrogenase
MscR, which suggests that Mno is sufficient to dissimilate methanol and the resulting formaldehyde
in vivo
Finally, we show that
M. smegmatis
devoid of
phosphoenolpyruvate carboxykinase
, which has been shown to fix CO
2
in
M. tuberculosis
, does not grow on methanol, suggesting that the final step of methanol utilization requires CO
2
fixation for biomass generation. Our work here thus forms the first comprehensive report that explores methylotrophy in a mycobacterial species.
IMPORTANCE
Methylotrophy, the ability to utilize single-carbon (C
1
) compounds as the sole carbon and energy sources, is only poorly understood in mycobacteria. Both pathogenic and nonpathogenic mycobacteria, including
Mycobacterium tuberculosis
, are capable of utilizing C
1
compounds to meet their carbon and energy requirements, although the precise pathways are not well studied. Here we present a comprehensive study of methylotrophy in
Mycobacterium smegmatis
With several genetic knockouts, we have dissected the entire methanol metabolism pathway in
M. smegmatis
We show that while methanol dissimilation in
M. smegmatis
differs from that in other mycobacterial species, the concluding step of CO
2
fixation is similar to that in
M. tuberculosis
It is therefore both interesting and important to examine mycobacterial physiology in the presence of alternative carbon sources.
...
PMID:Methylotrophy in Mycobacteria: Dissection of the Methanol Metabolism Pathway in Mycobacterium smegmatis. 2989 42
