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Biochemistry

The surprising history of an antioxidant

Nature volume 551, pages 37–38 (2017)Cite this article

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What came first: oxygen-producing photosynthesis, or compounds that protect cells from oxygen-induced damage? It emerges that one such compound might have been produced in microbes before Earth's oxygenation.

The biosynthesis of ergothioneine was previously thought to require an aerobic environment. Its assembly occurs through a series of chemical transformations, beginning with the amino acid histidine3,4,5,6,7. The first step in this pathway adds three methyl groups to the amino group of histidine, to form an intermediate called hercynine (Fig. 1a). In fungal ergothioneine producers, such as Neurospora crassa, the enzyme Egt1 then catalyses the oxidation of hercynine and the amino acid cysteine, and combines them to form a sulfoxide intermediate (Fig. 1b); the cysteine is the source of the sulfur atom that ends up in ergothioneine. A similar oxidative process is catalysed by the enzymes EgtB and EgtC in bacteria such as Mycobacterium smegmatis, with the peptide γ-glutamylcysteine serving as the sulfur donor. In both fungi and bacteria, molecular oxygen is needed to accept the four electrons that are liberated during these oxidation reactions — which means that the conversion of hercynine to the sulfoxide requires an aerobic environment.

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Figure 1: Biosynthetic pathways to ergothioneine.

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Authors and Affiliations

  1. Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, 78712, Texas, USA

    Mark W. Ruszczycky

  2. Department of Chemistry, University of Texas, Austin

    Hung-wen Liu

Authors
  1. Mark W. Ruszczycky
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  2. Hung-wen Liu
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Correspondence to Mark W. Ruszczycky.

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Ruszczycky, M., Liu, Hw. The surprising history of an antioxidant. Nature 551, 37–38 (2017). https://doi.org/10.1038/551037a

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