Featured
-
-
Article
| Open AccessAkt and STAT5 mediate naïve human CD4+ T-cell early metabolic response to TCR stimulation
T-cell subsets differ in metabolic requirements for particular tasks. Here the authors characterize metabolic fluxes in naïve human CD4+ cells upon activation, and identify a role of Stat5 in glutaminolysis linked to IL-2 production.
- Nicholas Jones
- , Emma E. Vincent
- & Catherine A. Thornton
-
Article
| Open AccessA revised biosynthetic pathway for the cofactor F420 in prokaryotes
Cofactor F420 plays crucial roles in bacterial and archaeal metabolism, but its biosynthetic pathway is not fully understood. Here, the authors present the structure of one of the enzymes and provide experimental evidence for a substantial revision of the pathway, including the identification of a new intermediate.
- Ghader Bashiri
- , James Antoney
- & Colin J. Jackson
-
Article
| Open AccessA bacterial checkpoint protein for ribosome assembly moonlights as an essential metabolite-proofreading enzyme
Adventitious oxidation of erythrose-4-phosphate generates 4-phosphoerythronate, which is detoxified by metabolite-proofreading phosphatases in eukaryotes. Here, Sachla & Helmann show that a similar function is carried out in Bacillus subtilis by a checkpoint protein involved in ribosome assembly.
- Ankita J. Sachla
- & John D. Helmann
-
Article
| Open AccessSpatial-fluxomics provides a subcellular-compartmentalized view of reductive glutamine metabolism in cancer cells
Measuring metabolic fluxes in cellular compartments is a challenge. Here, the authors introduce an approach to infer fluxes in mitochondria and cytosol, and find that IDH1 is the major producer of cytosolic citrate in HeLa cells and that in SDH- deficient cells citrate synthase functions in reverse.
- Won Dong Lee
- , Dzmitry Mukha
- & Tomer Shlomi
-
Article
| Open AccessPhototrophic extracellular electron uptake is linked to carbon dioxide fixation in the bacterium Rhodopseudomonas palustris
Extracellular electron uptake (EEU) is the ability of microbes to take up electrons from solid-phase conductive substances such as metal oxides. Here, Guzman et al. show that electrons enter the photosynthetic electron transport chain and are used for CO2 fixation during EEU in a phototrophic bacterium.
- Michael S. Guzman
- , Karthikeyan Rengasamy
- & Arpita Bose
-
Article
| Open AccessSerine synthesis through PHGDH coordinates nucleotide levels by maintaining central carbon metabolism
Serine synthesis from glucose is required even when serine is available from the environment. Here, the authors explain this paradox by showing that the enzyme PHGDH enables nucleotide synthesis by coordinating anabolic fluxes related to central carbon metabolism, independent of its role in serine production.
- Michael A. Reid
- , Annamarie E. Allen
- & Jason W. Locasale
-
Article
| Open AccessAn electrogenic redox loop in sulfate reduction reveals a likely widespread mechanism of energy conservation
The bacterial complex QrcABCD plays a key role in the bioenergetics of sulfate respiration. Here, Duarte et al. show that this complex is electrogenic, with protons and electrons required for quinone reduction being extracted from opposite sides of the membrane.
- Américo G. Duarte
- , Teresa Catarino
- & Inês A. C. Pereira
-
Article
| Open AccessA modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds
Assimilating the abundant one-carbon compounds by an industrially-relevant microorganism can broaden the substrate range and achieve reactions that are difficult for chemical process. Here the authors show a modified serine cycle can convert methanol and CO2 to two-carbon compounds in an engineered E. coli strain.
- Hong Yu
- & James C. Liao
-
Article
| Open AccessEvolution of gene knockout strains of E. coli reveal regulatory architectures governed by metabolism
The function of metabolic genes in the context of regulatory networks is not well understood. Here, the authors investigate the adaptive responses of E. coli after knockout of metabolic genes and highlight the influence of metabolite levels in the evolution of regulatory function.
- Douglas McCloskey
- , Sibei Xu
- & Bernhard O. Palsson
-
Article
| Open AccessSalvage of the 5-deoxyribose byproduct of radical SAM enzymes
5-Deoxyribose is formed from 5′-deoxyadenosine, a toxic byproduct of radical S-adenosylmethionine enzymes. Here, the authors identify and biochemically characterize a bacterial salvage pathway for 5-deoxyribose, consisting of three enzymes, and solve the crystal structure of the key aldolase.
- Guillaume A. W. Beaudoin
- , Qiang Li
- & Andrew D. Hanson
-
Article
| Open AccessAlternative assembly of respiratory complex II connects energy stress to metabolic checkpoints
Mitochondrial complex II is normally composed of four subunits. Here the authors show that bioenergetic stress conditions give rise to a partially assembled variant of complex II, which shifts the anabolic pathways to less energy demanding processes.
- Ayenachew Bezawork-Geleta
- , He Wen
- & Jiri Neuzil
-
Article
| Open AccessIncreased glutarate production by blocking the glutaryl-CoA dehydrogenation pathway and a catabolic pathway involving l-2-hydroxyglutarate
It is known that the five carbon platform chemical glutarate can be catabolized by the glutaryl-CoA dehydrogenation pathway. Here, the authors discover an additional glutarate catabolic pathway involving l-2-hydroxyglutarate and show increased glutarate production by blocking both catabolic pathways.
- Manman Zhang
- , Chao Gao
- & Ping Xu
-
Article
| Open AccessIncreased formate overflow is a hallmark of oxidative cancer
Serine catabolism to formate supplies one-carbon units for biosynthesis. Here the authors show that formate production in murine cancers with high oxidative metabolism exceeds the biosynthetic demand and that high formate levels promotes invasion of cancer cells.
- Johannes Meiser
- , Anne Schuster
- & Alexei Vazquez
-
Article
| Open AccessMutual potentiation drives synergy between trimethoprim and sulfamethoxazole
The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMX) synergistically inhibit bacterial tetrahydrofolate biosynthesis, apparently because SMX potentiates TMP activity. Here, Minato et al. identify a metabolic feedback loop in this pathway, revealing that TMP also potentiates SMX activity.
- Yusuke Minato
- , Surendra Dawadi
- & Anthony D. Baughn
-
Article
| Open AccessEngineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches
Breviscapine is the flavonoid extract from medical plant Erigeron breviscapus for the treatment of cardio- and cerebrovascular disease. Here, the authors identify the key enzymes of the biosynthetic pathway from the plant genome and engineer yeast to produce breviscapine from glucose.
- Xiaonan Liu
- , Jian Cheng
- & Huifeng Jiang
-
Article
| Open AccessLinked cycles of oxidative decarboxylation of glyoxylate as protometabolic analogs of the citric acid cycle
The citric acid cycle (TCA) is a fundamental metabolic pathway to release stored energy in living organisms. Here, the authors report two linked cycles of reactions that each oxidize glyoxylate into CO2 and generate intermediates shared with the modern TCA cycle, shedding light into a plausible TCA protometabolism.
- Greg Springsteen
- , Jayasudhan Reddy Yerabolu
- & Ramanarayanan Krishnamurthy
-
Article
| Open AccessPeritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels
Tissue-resident marcophages have both generic and tissue-specific functions, but how the latter functions are imbued is still unclear. Here the authors show that peritoneal macrophages express a specialised genetic programme to utilise the locally enriched glutamate for a metabolic setting that facilitates protective in situ immunity.
- Luke C. Davies
- , Christopher M. Rice
- & Daniel W. McVicar
-
Article
| Open AccessA synthetic biochemistry platform for cell free production of monoterpenes from glucose
Terpenes are bioactive natural products derived from plants with several commercial applications. Here, the authors engineer a cell-free system composed of 27 enzymes that convert glucose into terpenes, highlighting the potential of synthetic biochemistry approaches for biocompounds production.
- Tyler P. Korman
- , Paul H. Opgenorth
- & James U. Bowie
-
Article
| Open AccessInhibition of hepatic lipogenesis enhances liver tumorigenesis by increasing antioxidant defence and promoting cell survival
The lipogenic pathway is often upregulated in liver tumours and regarded as a therapeutic target. Here, the authors show instead that blocking lipogenesis via knockout of acetyl-CoA carboxylase genes results in increased susceptibility to liver tumorigenesis associated with an increased antioxidant defence.
- Marin E. Nelson
- , Sujoy Lahiri
- & Kyle L. Hoehn
-
Article
| Open AccessEnzyme I facilitates reverse flux from pyruvate to phosphoenolpyruvate in Escherichia coli
Enzyme I, a component of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS), converts phosphoenolpyruvate to pyruvate. Here, the authors show that Enzyme I facilitates also the reverse reaction during both gluconeogenic and glycolytic growth inE. coli.
- Christopher P. Long
- , Jennifer Au
- & Maciek R. Antoniewicz
-
Article
| Open AccessA RuBisCO-mediated carbon metabolic pathway in methanogenic archaea
Although not photosynthetic, some archaea possess RuBisCO, one of the enzymes characteristic of the photosynthetic Calvin-Benson cycle, but apparently lack another one, phosphoribulokinase (PRK). Here the authors describe a carbon metabolic pathway in methanogenic archaea, involving RuBisCO and PRK.
- Takunari Kono
- , Sandhya Mehrotra
- & Hiroki Ashida
-
Article
| Open AccessNRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Raising cellular levels of the metabolic cofactor NAD+ reverses key indicators of aging. Here, Ratajczak et al. show that cellular levels of NAD+ depend on the extracellular catalytic activity of NRK1, which processes two NAD+precursors, nicotinamide mononucleotide and nicotinamide riboside, in mice.
- Joanna Ratajczak
- , Magali Joffraud
- & Carles Cantó
-
Article
| Open AccessTurning the respiratory flexibility of Mycobacterium tuberculosis against itself
Several inhibitors of the electron transport chain (ETC) are active against Mycobacterium tuberculosis. Here, Lamprecht et al. show that a combination of known inhibitors (bedaquiline, Q203 and clofazimine) displays synergistic effects on the M. tuberculosis ETC and improved antibacterial activity in vitro.
- Dirk A. Lamprecht
- , Peter M. Finin
- & Adrie J. C. Steyn
-
Article
| Open AccessLight-driven oxidation of polysaccharides by photosynthetic pigments and a metalloenzyme
Lytic polysaccharide monooxygenases are proteins involved in the degradation of plant biomass and are promising biotechnological tools for biofuel production. Here, the authors show that their catalytic activity is significantly boosted when they are combined with photopigments and exposed to light.
- D. Cannella
- , K. B. Möllers
- & C. Felby
-
Article
| Open AccessLower glycolysis carries a higher flux than any biochemically possible alternative
The biochemical pathways of central carbon metabolism are highly conserved across all domains of life. Here, Courtet al. use a computational approach to test all possible pathways of glycolysis and gluconeogenesis and find that the existing trunk pathways may represent a maximal flux solution selected for during evolution.
- Steven J. Court
- , Bartlomiej Waclaw
- & Rosalind J. Allen
-
Article
| Open AccessTwo enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis
Mycobacterium tuberculosis feeds on host fatty acids during infection, a process that requires a fructose bisphosphatase (FBPase) enzyme for gluconeogenesis. Here, Ganapathy et al.show that the bacterium has two different FBPases and that this enzymatic activity is required for full virulence.
- Uday Ganapathy
- , Joeli Marrero
- & Sabine Ehrt
-
Article
| Open AccessPharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis
Adverse drug reactions are an important clinical problem. Here the authors combine information about drug-induced gene expression changes and genetic variability of patients with a genome-scale metabolic model to identify drug-induced changes in cellular metabolism that may be linked to drug side effects.
- Daniel C. Zielinski
- , Fabian V. Filipp
- & Bernhard O. Palsson
-
Article |
A synthetic biochemistry molecular purge valve module that maintains redox balance
In vitro biochemical pathways could provide the high yields required for economical commodity chemical production, but require circuitry development to regulate high-energy cofactors. Here, the authors design and test a simple purge valve system to maintain NADP+/NADPH balance in E. coli.
- Paul H. Opgenorth
- , Tyler P. Korman
- & James U. Bowie
-
Article |
A high-energy-density sugar biobattery based on a synthetic enzymatic pathway
Incomplete oxidation of fuels is a common problem in enzymatic fuel cells and it leads to low energy densities. Zhu et al. report the complete oxidation of sugar in an enzymatic fuel cell through a synthetic enzymatic pathway, which exhibits higher energy densities than lithium-ion batteries.
- Zhiguang Zhu
- , Tsz Kin Tam
- & Y. -H. Percival Zhang
-
Article |
Dynamic optimization identifies optimal programmes for pathway regulation in prokaryotes
The ability to induce metabolic pathways in response to a changing environment is an important component of bacterial fitness. Bartl et al. identify optimal programmes for metabolic pathway activation depending on protein synthesis capacity constraints, and demonstrate their impact on operonic organization.
- Martin Bartl
- , Martin Kötzing
- & Christoph Kaleta
-
Article
| Open AccessDendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties
It has been hypothesized that the steroidal alkaloid dendrogenin A (DDA) is a natural metabolite. de Medina et al.show that DDA is produced in mammalian tissues from 5,6α-epoxy-cholesterol and histamine metabolism, and that the compound displays cell differentiation and anti-tumour activities.
- Philippe de Medina
- , Michael R. Paillasse
- & Marc Poirot
-
Article |
Synthetic RNA devices to expedite the evolution of metabolite-producing microbes
Genome-wide variation in the directed evolution of metabolite-overproducing microbes requires high-throughput screening platforms. Yang et al.show that synthetic RNA devices can sense target metabolites, enrich pathway optimisation, and expedite the evolution of metabolite-producing microbes.
- Jina Yang
- , Sang Woo Seo
- & Gyoo Yeol Jung
-
Article
| Open AccessBlimp1 regulates the transition of neonatal to adult intestinal epithelium
Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.
- Vanesa Muncan
- , Jarom Heijmans
- & Gijs R. van den Brink
-
Article
| Open AccessStructural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly
Frataxin is an essential protein that has been linked to iron–sulphur cluster assembly, and reduced levels are associated with Friedrich's ataxia. In this study, a combination of techniques is used to probe the interactions of the bacterial frataxin orthologue CyaY with the iron–sulphur cluster assembly machinery.
- Filippo Prischi
- , Petr V. Konarev
- & Annalisa Pastore