Evolutionary adaptations that enable enzymes to tolerate oxidative stress

Imlay, James A.; Ramakrishnan, Sethu; Rohaun, Sanjay Kumar

doi:10.1016/j.freeradbiomed.2019.01.048

Cited by 41 publications

(28 citation statements)

References 77 publications

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“…Enzymes adapted against oxidative stress have developed tolerance mechanisms that include shielding vulnerable metal centers by accessory domains, evolving of iron cofactors into less oxidizable forms, and replacement of iron with alternative metal ions. (8).…”

mentioning

confidence: 99%

Cellular responses to reactive oxygen species are predicted from molecular mechanisms

Yang

Mih

Anand

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a computable multiscale description of the ROS stress response inEscherichia coli, called OxidizeME. We use OxidizeME to explain four key responses to oxidative stress: 1) ROS-induced auxotrophy for branched-chain, aromatic, and sulfurous amino acids; 2) nutrient-dependent sensitivity of growth rate to ROS; 3) ROS-specific differential gene expression separate from global growth-associated differential expression; and 4) coordinated expression of iron–sulfur cluster (ISC) and sulfur assimilation (SUF) systems for iron–sulfur cluster biosynthesis. These results show that we can now develop fundamental and quantitative genotype–phenotype relationships for stress responses on a genome-wide basis.

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confidence: 99%

Cellular responses to reactive oxygen species are predicted from molecular mechanisms

Yang

Mih

Anand

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Accordingly, increasing the level (via pre-culture) or maintenance (MSR overexpression) of reduced Met should help to keep FeS clusters intact in oxidizing cellular environments. Oxidative stress in general is well known to target surface-exposed FeS clusters in proteins ( Imlay et al, 2019 ). FeS proteins are highly reactive with FAC ( Albrich et al, 1981 ) and NaOCl may, potentially via ROS generation in cells, damage the clusters in bacterial FeS proteins ( Romsang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of fungi with FAC or other reactive oxygen species (ROS) promotes oxidative stress and oxidative damage to cellular macromolecules (Avery, 2011;Carmona-Gutierrez et al, 2013). One key molecular target of oxidative stress is iron-sulfur (FeS) cluster proteins (Imlay et al, 2019). FeS-cofactors are found in proteins required for diverse cellular functions, including translation, protein regulation, citric acid cycle, mitochondrial electron transport chain and DNA binding (Cardenas-Rodriguez et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Top-Down Characterization of an Antimicrobial Sanitizer, Leading From Quenchers of Efficacy to Mode of Action

Wohlgemuth¹,

Gomes²,

Singleton³

et al. 2020

Front. Microbiol.

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We developed a top-down strategy to characterize an antimicrobial, oxidizing sanitizer, which has diverse proposed applications including surface-sanitization of fresh foods, and with benefits for water resilience. The strategy involved finding quenchers of antimicrobial activity then antimicrobial mode of action, by identifying key chemical reaction partners starting from complex matrices, narrowing down reactivity to specific organic molecules within cells. The sanitizer electrolyzed-water (EW) retained partial fungicidal activity against the food-spoilage fungus Aspergillus niger at high levels of added soils (30-750 mg mL −1), commonly associated with harvested produce. Soil with high organic load (98 mg g −1) gave stronger EW inactivation. Marked inactivation by a complex organics mix (YEPD medium) was linked to its protein-rich components. Addition of pure proteins or amino acids (≤1 mg mL −1) fully suppressed EW activity. Mechanism was interrogated further with the yeast model, corroborating marked suppression of EW action by the amino acid methionine. Pre-culture with methionine increased resistance to EW, sodium hypochlorite, or chlorine-free ozonated water. Overexpression of methionine sulfoxide reductases (which reduce oxidized methionine) protected against EW. Fluoroprobe-based analyses indicated that methionine and cysteine inactivate free chlorine species in EW. Intracellular methionine oxidation can disturb cellular FeS-clusters and we showed that EW treatment impairs FeS-enzyme activity. The study establishes the value of a top-down approach for multi-level characterization of sanitizer efficacy and action. The results reveal proteins and amino acids as key quenchers of EW activity and, among the amino acids, the importance of methionine oxidation and FeS-cluster damage for antimicrobial mode-of-action.

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“…The idea that evolution has tinkered with fumarase to adjust its sensitivity to oxidants conforms with similar observations of other ROS-sensitive enzyme classes. Chloroplasts, which are sites of photosynthetic ROS formation, cofactor their IPMI enzymes with stable [2Fe–2S] clusters rather than the unstable [4Fe–4S] variety [54]. The other primary target of H 2 O 2 inside cells are mononuclear enzymes that employ a single divalent transition metal to catalyze non-redox reactions.…”

Section: Discussionmentioning

confidence: 99%

A conserved motif liganding the [4Fe–4S] cluster in [4Fe–4S] fumarases prevents irreversible inactivation of the enzyme during hydrogen peroxide stress

Imlay

2019

Redox Biology

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Organisms have evolved two different classes of the ubiquitous enzyme fumarase: the [4Fe–4S] cluster-containing class I enzymes are oxidant-sensitive, whereas the class II enzymes are iron-free and therefore oxidant-resistant. When hydrogen peroxide (H2O2) attacks the most-studied [4Fe–4S] fumarases, only the cluster is damaged, and thus the cell can rapidly repair the enzyme. However, this study shows that when elevated levels of H2O2 oxidized the class I fumarase of the obligate anaerobe Bacteroides thetaiotaomicron (Bt-Fum), a hydroxyl-like radical species was produced that caused irreversible covalent damage to the polypeptide. Unlike the fumarase of oxygen-tolerant bacteria, Bt-Fum lacks a key cysteine residue in the typical “CXnCX2C″ motif that ligands [4Fe–4S] clusters. Consequently H2O2 can access and oxidize an iron atom other than the catalytic one in its cluster. Phylogenetic analysis showed that certain clades of bacteria may have evolved the full “CXnCX2C″ motif to shield the [4Fe–4S] cluster of fumarase. This effect was reproduced by the construction of a chimeric enzyme. These data demonstrate the irreversible oxidation of Fe–S cluster enzymes and may recapitulate evolutionary steps that occurred when microorganisms originally confronted oxidizing environments. It is also suggested that, if H2O2 is generated within the colon as a consequence of inflammation or the action of lactic acid bacteria, the inactivation of fumarase could potentially impair the central fermentation pathway of Bacteroides species and contribute to gut dysbiosis.

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Evolutionary adaptations that enable enzymes to tolerate oxidative stress

Cited by 41 publications

References 77 publications

Cellular responses to reactive oxygen species are predicted from molecular mechanisms

Cellular responses to reactive oxygen species are predicted from molecular mechanisms

Top-Down Characterization of an Antimicrobial Sanitizer, Leading From Quenchers of Efficacy to Mode of Action

A conserved motif liganding the [4Fe–4S] cluster in [4Fe–4S] fumarases prevents irreversible inactivation of the enzyme during hydrogen peroxide stress

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