Alternate Antioxidant Pathway

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Science  04 Feb 2011:
Vol. 331, Issue 6017, pp. 513
DOI: 10.1126/science.331.6017.513-c

The low-molecular-weight thiol glutathione (GSH) is essential for growth in eukaryotes and plays a central role in stress responses and the maintenance of redox homeostasis in certain bacteria. Surprisingly, most aerobic bacteria lack the GSH biosynthesis enzyme glutamate cysteine ligase (GshA), although many have genes encoding proteins expected to require GSH for activity. To understand how these bacteria thrive, Veeravalli et al. isolated suppressor mutations in GshA-deficient Escherichia coli cells that expressed GSH. These cells carried mutations in the first two genes in the proline biosynthesis pathway, proB and proA. The mutations facilitated the accumulation of γ-glutamyl phosphate. This reacts with cysteine to give γ-glutamyl cysteine, which is converted to GSH by the enzyme glutathione synthase. Bioinformatic analysis revealed homologs of the suppressor ProB in bacterial strains that make GSH-dependent proteins but do not encode GshA. These results suggest that the proline biosynthetic pathway may have a role in GSH synthesis in prokaryotes.

Nat. Chem. Biol. 7, 101 (2011).

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