Condensate Formation by Metabolic Enzymes in Saccharomyces cerevisiae

Miura, Naruhisa

doi:10.3390/microorganisms10020232

Cited by 6 publications

(4 citation statements)

References 63 publications

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“…The growth defect of ADH1 -knockout cells was recovered by the introduction of plasmids for overexpressing ADH1 (S4 Fig in S1 File ), suggesting that the growth defect was due to the non-existence of ADH1 . Most enzymes of the glycolytic pathway that catalyze the metabolism of glucose to acetaldehyde and acetaldehyde to acetic acid are known to form condensates under hypoxia, while enzymes involved in glycerol and ethanol synthesis do not [ 9 ] (4B Fig). If the localization of Adh1p to intracellular META bodies or other condensates has no effect on cell metabolism, then the production of ethanol from glucose and the ratio of ethanol to acetic acid in culture media should be unchanged.…”

Section: Resultsmentioning

confidence: 99%

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Foci-forming regions of pyruvate kinase and enolase at the molecular surface incorporate proteins into yeast cytoplasmic metabolic enzymes transiently assembling (META) bodies

et al. 2023

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Spatial reorganization of metabolic enzymes to form the “metabolic enzymes transiently assembling (META) body” is increasingly recognized as a mechanism contributing to regulation of cellular metabolism in response to environmental changes. A number of META body-forming enzymes, including enolase (Eno2p) and phosphofructokinase, have been shown to contain condensate-forming regions. However, whether all META body-forming enzymes have condensate-forming regions or whether enzymes have multiple condensate-forming regions remains unknown. The condensate-forming regions of META body-forming enzymes have potential utility in the creation of artificial intracellular enzyme assemblies. In the present study, the whole sequence of yeast pyruvate kinase (Cdc19p) was searched for condensate-forming regions. Four peptide fragments comprising 27–42 amino acids were found to form condensates. Together with the fragment previously identified from Eno2p, these peptide regions were collectively termed “META body-forming sequences (METAfos).” METAfos-tagged yeast alcohol dehydrogenase (Adh1p) was found to co-localize with META bodies formed by endogenous Cdc19p under hypoxic conditions. The effect of Adh1p co-localization with META bodies on cell metabolism was further evaluated. Expression of Adh1p fused with a METAfos-tag increased production of ethanol compared to acetic acid, indicating that spatial reorganization of metabolic enzymes affects cell metabolism. These results contribute to understanding of the mechanisms and biological roles of META body formation.

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Section: Resultsmentioning

confidence: 99%

“…Other enzymes, including purine biosynthetic enzymes, are known to form condensates termed the “Purinosome” in human-derived HeLa cells [ 7 , 8 ]. These multiple condensates of metabolic enzymes are collectively referred to as the “metabolic enzymes transiently assembling (META) body” [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Foci-forming regions of pyruvate kinase and enolase at the molecular surface incorporate proteins into yeast cytoplasmic metabolic enzymes transiently assembling (META) bodies

et al. 2023

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“…We have previously shown that the negatively charged l -lactate oxidase (LOX, p I = 6) can form enzyme assemblies in the presence of the positively charged poly- l -lysine (PLL), a polyelectrolyte that mimics IDRs at physiological pH, and trigger the activation of LOX 14 . Enzyme assemblies have been investigated as a mechanism of intracellular enzymatic activation 15 , 16 . The size of an enzyme assembly is important for enzyme activation 14 .…”

Section: Introductionmentioning

confidence: 99%

Activation of oxidoreductases by the formation of enzyme assembly

Ura,

Sakakibara,

Hirano

et al. 2023

Sci Rep

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Biological properties of protein molecules depend on their interaction with other molecules, and enzymes are no exception. Enzyme activities are controlled by their interaction with other molecules in living cells. Enzyme activation and their catalytic properties in the presence of different types of polymers have been studied in vitro, although these studies are restricted to only a few enzymes. In this study, we show that addition of poly-l-lysine (PLL) can increase the enzymatic activity of multiple oxidoreductases through formation of enzyme assemblies. Oxidoreductases with an overall negative charge, such as l-lactate oxidase, d-lactate dehydrogenase, pyruvate oxidase, and acetaldehyde dehydrogenase, each formed assemblies with the positively charged PLL via electrostatic interactions. The enzyme activities of these oxidoreductases in the enzyme assemblies were several-folds higher than those of the enzyme in their natural dispersed state. In the presence of PLL, the turnover number (kcat) improved for all enzymes, whereas the decrease in Michaelis constant (KM) was enzyme dependent. This type of enzyme function regulation through the formation of assemblies via simple addition of polymers has potential for diverse applications, including various industrial and research purposes.

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“…b Unless mentioned otherwise, original references for the various enzymes can be found in comprehensive reviews by Park and Horton [15] and Montrose et al, [30] as well as more focused reviews. [6,17,18,[31][32][33][34][35][36][37] c See Reference [38]. d See References [39,40], and [41].…”

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confidence: 99%

Biochemical communication between filament‐forming enzymes

Bearne

2024

BioEssays

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A host of metabolic enzymes reversibly self‐assemble to form membrane‐less, intracellular filaments under normal physiological conditions and in response to stress. Often, these enzymes reside at metabolic control points, suggesting that filament formation affords an additional regulatory mechanism. Examples include cytidine‐5′‐triphosphate (CTP) synthase (CTPS), which catalyzes the rate‐limiting step for the de novo biosynthesis of CTP; inosine‐5′‐monophosphate dehydrogenase (IMPDH), which controls biosynthetic access to guanosine‐5′‐triphosphate (GTP); and ∆1‐pyrroline‐5‐carboxylate (P5C) synthase (P5CS) that catalyzes the formation of P5C, which links the Krebs cycle, urea cycle, and proline metabolism. Intriguingly, CTPS can exist in co‐assemblies with IMPDH or P5CS. Since GTP is an allosteric activator of CTPS, the association of CTPS and IMPDH filaments accords with the need to coordinate pyrimidine and purine biosynthesis. Herein, a hypothesis is presented furnishing a biochemical connection underlying co‐assembly of CTPS and P5CS filaments – potent inhibition of CTPS by glutamate γ‐semialdehyde, the open‐chain form of P5C.

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Condensate Formation by Metabolic Enzymes in Saccharomyces cerevisiae

Cited by 6 publications

References 63 publications

Foci-forming regions of pyruvate kinase and enolase at the molecular surface incorporate proteins into yeast cytoplasmic metabolic enzymes transiently assembling (META) bodies

Foci-forming regions of pyruvate kinase and enolase at the molecular surface incorporate proteins into yeast cytoplasmic metabolic enzymes transiently assembling (META) bodies

Activation of oxidoreductases by the formation of enzyme assembly

Biochemical communication between filament‐forming enzymes

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