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Global cellular metabolic rewiring adapts Corynebacterium glutamicum to efficient non-natural substrate utilization

ABSTRACT: Global cellular metabolic rewiring adapts Corynebacterium glutamicum to efficient non-natural substrate utilization

PROVIDER: PRJNA764518 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15964634_1.fastq.gz	Fastqsanger.gz
	SRR15964634_2.fastq.gz	Fastqsanger.gz
	SRR15964635_1.fastq.gz	Fastqsanger.gz
	SRR15964635_2.fastq.gz	Fastqsanger.gz
	SRR15964636_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Global cellular metabolic rewiring adapts Corynebacterium glutamicum to efficient non-natural substrate utilization

Project description:Efficient assimilation of renewable feedstocks is the cornerstone for achieving sustainable and economical microbial production of commodity chemicals. Unfortunately, most renewables are foreign to the cellular metabolism of classical industrial workhorses, resulting in unsatisfactory biomanufacturing performance. Here, Corynebacterium glutamicum was systematically engineered for rapid non-natural xylose metabolism and the underlying adaptations were elucidated by combining metabolic engineering, adaptive laboratory evolution and systems biology techniques. A plasmid-free, stable and efficient xylose-utilizing chassis strain, named CGS15, was reconstructed with both a rapid specific growth rate of 0.341 h-1 on xylose and an excellent co-utilization of glucose and xylose at a ratio of about 2:1. For the first time, we revealed a novel xylose regulatory mechanism by the endogenous transcription factor IpsA with global regulatory effects on C. glutamicum core carbon and energy metabolism. The coordination between the heterologous xylose metabolism and the endogenous carbon/energy metabolism both endowed cells with accelerated growth and released carbon catabolite repression. Finally, this chassis demonstrated great promise for lignocellulosic biorefinery applications by producing 97.1 g/L of the platform compound succinate from corn stalk hydrolysate with an average productivity of 8.09 g/L/h. This work provides an elegant paradigm to understand and engineer the metabolism of renewable substrates for sustainable biomanufacturing.

2022-10-03 | GSE184402 | GEO

Global Cellular Metabolic Rewiring Adapts Corynebacterium glutamicum to Efficient Nonnatural Xylose Utilization.

Project description: Not available

| S-EPMC9746319 | biostudies-literature

Project description:Global cellular metabolic rewiring adapts Corynebacterium glutamicum to efficient non-natural substrate utilization

| PRJNA763329 | ENA

YAP rejuvenates cardiomyocytes by changing mitochondrial substrate utilization

Project description:Postnatal cardiomyocyte (CM) maturation, marked by a metabolic transition from glycolysis to fatty acid oxidation, impedes adult CM proliferation and heart regeneration. Our research reveals that Hippo-YAP signaling facilitates CM cell cycle re-entry by reducing lipid utilization in CMs, thereby preserving mitochondrial homeostasis, and promoting CM rejuvenation. On the other hand, overloaded fat by a maternal high-fat diet significantly enhances fatty acid oxidation and maturation in neonatal CMs, counteracting YAP-mediated rejuvenation effects. Through metabolomic and transcriptomic analyses, we discovered that YAP-induced mitochondrial substrate utilization change predominantly depends on reducing Cpt1b activity. Additionally, we identified Mef2 as a crucial activator for CM maturation, which is inhibited upon YAP overexpression, leading to decreased Cpt1b levels in CMs. Our results highlight the heterogeneity and adaptability of neonatal CM energy metabolism and establish YAP as a key regulator of CM substrate utilization. Furthermore, we elucidate a mechanistic framework by which YAP reverses metabolic maturation in cardiomyocytes, thereby facilitating heart regeneration. This insight advances our understanding of metabolic remodeling in heart regeneration and the therapeutic potential of YAP.

2026-04-21 | GSE262046 | GEO

YAP rejuvenates cardiomyocytes by changing mitochondrial substrate utilization

Project description:YAP rejuvenates cardiomyocytes by changing mitochondrial substrate utilization

| PRJNA1090093 | ENA

Determination of transcriptional start sites in the presence of GABA for Corynebacterium glutamicum

Project description:In this study, we analyzed the regulation of ƴ-aminobutyrate (GABA) utilization in Corynebacterium glutamicum by the PucR-type transcriptional regulator GabR and by alternative nitrogen and carbon sources.

2020-09-29 | GSE156688 | GEO

Metabolic Rewiring by Acetate Promotes Efficient Xylose Utilization in Rhodotorula toruloides

Project description:Metabolic Rewiring by Acetate Promotes Efficient Xylose Utilization in Rhodotorula toruloides

| PRJNA1208580 | ENA

Ciprofloxacin triggers L-glutamate production by Corynebacterium glutamicum

Project description:Ciprofloxacin, an inhibitor of bacterial gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum with concomitant excretion of L-glutamate. C. glutamicum strains overproducing L-lysine, L-arginine, L-ornithine, and putrescine, respectively, produced L-glutamate instead of the desired amino acid when exposed to ciprofloxacin. Even in the absence of the putative L-glutamate exporter gene yggB, ciprofloxacin effectively triggered L-glutamate production. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than L-glutamate was produced as consequence of exposure to ciprofloxacin. Transcriptome analysis revealed that ciprofloxacin increased RNA levels of genes involved in DNA synthesis, repair and modification. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition. Here, it was shown for the first time that production of L-glutamate by C. glutamicum may be triggered by an inhibitor of DNA synthesis and L-glutamate titers of up to 37 ± 1 mM and a substrate specific L-glutamate yield of 0.13 g/g were reached.

2016-01-26 | GSE77189 | GEO

PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.

Project description:The role of peroxisome proliferator-activated receptor δ (PPARδ) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPARδ agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPARδ activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPARδ activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation. Keywords: Expression profiling by array

2014-05-23 | GSE40789 | GEO

Control of heme homeostasis in Corynebacterium glutamicum by the two-component system HrrSA

Project description:The response regulator HrrA belonging to the HrrSA two-component system (previously named CgtSR11) is known to be repressed by the global iron-dependent regulator DtxR in Corynebacterium glutamicum. Sequence analysis indicated an involvement of the HrrSA system in heme-dependent gene expression. Growth experiments revealed that the non-pathogenic soil bacterium C. glutamicum is able to use hemin or hemoglobin as sole iron source. In DNA microarray analyses a putative operon encoding the hemin-binding protein HtaA and the putative hemin ABC transporter HmuTUV showed a strong upregulation in heme-grown cells. Deletion of the hmu operon clearly affects heme utilization, but does not completely abolish growth on heme or hemoglobin. As a central part of this study, we investigated the regulon of the response regulator HrrA via comparative transcriptome analysis of a hrrA deletion mutant and C. glutamicum wild type in combination with DNA-protein interaction studies with purified HrrA protein. Our data provide evidence for a heme-dependent transcriptional activation of heme oxygenase (hmuO), an enzyme involved in the utilization of heme as iron source. Besides hmuO, HrrA was shown to activate the expression of heme-containing components of the respiratory chain, namely ctaD and the ctaE-qcrCAB operon encoding subunits I and III of cytochrome aa3 oxidase and three subunits of the cytochrome bc1 complex. Furthermore, HrrA represses almost all genes involved in heme biosynthesis, including glutamyl-tRNA reductase (hemA), uroporphyrinogen decarboxylase (hemE), and ferrochelatase (hemH). Thus, our data clearly emphasize a central role of the HrrSA system in the control of heme homeostasis in C. glutamicum.

2010-12-17 | GSE26122 | GEO

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