Department of Chemistry, University of Basel, Mattenstrasse 24a, Basel 4002, Switzerland.
ACS Chem Biol. 2021 Feb 19;16(2):397-403. doi: 10.1021/acschembio.0c00968. Epub 2021 Feb 5.
Ergothioneine is a histidine-derived sulfur metabolite that is biosynthesized by bacteria and fungi. Plants and animals absorb ergothioneine as a micronutrient from their environment or nutrition. Several different mechanisms of microbial ergothioneine production have been described in the past ten years. Much less is known about the genetic and structural basis for ergothioneine catabolism. In this report, we describe the reconstitution of a five-step pathway that degrades ergothioneine to l-glutamate, trimethylamine, hydrogen sulfide, carbon dioxide, and ammonia. The first two steps are catalyzed by the two enzymes ergothionase and thiourocanate hydratase. These enzymes are closely related to the first two enzymes in histidine catabolism. However, the crystal structure of thiourocanate hydratase from the firmicute reveals specific structural features that strictly differentiate the activity of this enzyme from that of urocanate hydratases. The final two steps are catalyzed by metal-dependent hydrolases that share most homology with the last two enzymes in uracil catabolism. The early and late part of this pathway are connected by an entirely new enzyme type that catalyzes desulfurization of a thiohydantoin intermediate. Homologous enzymes are encoded in many soil-dwelling firmicutes and proteobacteria, suggesting that bacterial activity may have a significant impact on the environmental availability of ergothioneine.
麦硫因是一种由细菌和真菌生物合成的组氨酸衍生硫代谢物。植物和动物从环境或营养中吸收麦硫因作为微量营养素。在过去的十年中，已经描述了几种不同的微生物麦硫因生产机制。对于麦硫因分解的遗传和结构基础知之甚少。在本报告中，我们描述了重新构建的五步途径，该途径将麦硫因降解为 l-谷氨酸、三甲胺、硫化氢、二氧化碳和氨。前两步由两种酶，麦硫因酶和硫代尿酸水解酶催化。这些酶与组氨酸分解代谢的前两种酶密切相关。然而，来自厚壁菌的硫代尿酸水解酶的晶体结构揭示了严格区分该酶与尿刊酸水解酶活性的特定结构特征。最后两步由金属依赖性水解酶催化，这些水解酶与尿嘧啶分解代谢的最后两种酶具有最同源性。该途径的早期和晚期由一种全新的酶类型连接，该酶催化硫代海因中间物的脱硫。在许多土壤栖息的厚壁菌和变形菌中编码同源酶，表明细菌活性可能对麦硫因的环境可用性有重大影响。
