PMID:21521794
| Citation |
Feeney, MA, Veeravalli, K, Boyd, D, Gon, S, Faulkner, MJ, Georgiou, G and Beckwith, J (2011) Repurposing lipoic acid changes electron flow in two important metabolic pathways of Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 108:7991-6 |
|---|---|
| Abstract |
In bacteria, cysteines of cytoplasmic proteins, including the essential enzyme ribonucleotide reductase (RNR), are maintained in the reduced state by the thioredoxin and glutathione/glutaredoxin pathways. An Escherichia coli mutant lacking both glutathione reductase and thioredoxin reductase cannot grow because RNR is disulfide bonded and nonfunctional. Here we report that suppressor mutations in the lpdA gene, which encodes the oxidative enzyme lipoamide dehydrogenase required for tricarboxylic acid (TCA) cycle functioning, restore growth to this redox-defective mutant. The suppressor mutations reduce LpdA activity, causing the accumulation of dihydrolipoamide, the reduced protein-bound form of lipoic acid. Dihydrolipoamide can then provide electrons for the reactivation of RNR through reduction of glutaredoxins. Dihydrolipoamide is oxidized in the process, restoring function to the TCA cycle. Thus, two electron transfer pathways are rewired to meet both oxidative and reductive needs of the cell: dihydrolipoamide functionally replaces glutathione, and the glutaredoxins replace LpdA. Both lipoic acid and glutaredoxins act in the reverse manner from their normal cellular functions. Bioinformatic analysis suggests that such activities may also function in other bacteria. |
| Links |
PubMed PMC3093452 Online version:10.1073/pnas.1105429108 |
| Keywords |
Base Sequence; Citric Acid Cycle; Cytoplasm/metabolism; DNA Primers/genetics; DNA, Bacterial/genetics; Dihydrolipoamide Dehydrogenase/genetics; Dihydrolipoamide Dehydrogenase/metabolism; Electron Transport; Escherichia coli/genetics; Escherichia coli/growth & development; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Genes, Bacterial; Glutaredoxins; Glutathione Reductase/genetics; Glutathione Reductase/metabolism; Metabolic Networks and Pathways; Models, Biological; Mutation; Oxidation-Reduction; Ribonucleotide Reductases/genetics; Ribonucleotide Reductases/metabolism; Suppression, Genetic; Thioctic Acid/analogs & derivatives; Thioctic Acid/metabolism; Thioredoxin-Disulfide Reductase/genetics; Thioredoxin-Disulfide Reductase/metabolism |
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