Storage of the vital metal tungsten in a dominant SCFA-producing human gut microbe Eubacterium limosum and implications for other gut microbes.

IF 5.1 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-03-24 DOI:10.1128/mbio.02605-24
Nana Shao, Dayong Zhou, Gerrit J Schut, Farris L Poole, Sydney B Coffey, Aaron P Donaghy, Saisuki Putumbaka, Michael P Thorgersen, Lirong Chen, John Rose, Bi-Cheng Wang, Michael W W Adams
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引用次数: 0

Abstract

Enzymes containing tungsten rather than the ubiquitous and analogous element molybdenum are prevalent in the human gut microbiome, especifically in microbes that contribute to overall gut health. Eubacterium limosum is a dominant human gut organism whose production of beneficial short-chain fatty acids (SCFAs) from lactate involves tungstoenzymes. Here, we characterized E. limosum Tub, a tungsten storage protein. Tub has a sub-nanomolar affinity for tungstate and contains a single TOBE domain first characterized in a molybdate storage protein. Crystal structures revealed Tub assembles as a hexamer composed of a trimer of dimers, capable of binding eight tungstate oxyanions at two distinct binding sites located at inter-subunit interfaces. Tungstate-saturated Tub exhibited unusually high thermal and chemical stability. Glucose-grown E. limosum accumulates tungsten in Tub and has low levels of two tungstoenzymes, termed WOR1 and FDH, which oxidize aldehydes and formate, respectively. Lactate-grown cells contain high concentrations of these two tungstoenzymes where WOR1 and FDH are involved in converting lactate to SCFAs. Glucose-grown cells appear to accumulate tungstate in Tub in preparation for lactate availability in the human gut. Tub and other TOBE-containing proteins are widespread in the human gut microbiome, and gene co-occurrence analysis predicts that there are comparable numbers of TOBE-containing proteins involved in the storage of tungstate as there are that bind molybdate. The results with E. limosum represent an important step for understanding tungsten storage mechanisms for tungstoenzymes within human gut microbes in general.IMPORTANCETungsten metabolism was found to be prevalent in the human gut microbiome, which is involved in the detoxification of food and antimicrobial aldehydes, as well as in the production of beneficial SCFAs. In this study, we characterized a protein in the human gut microbe, Eubacterium limosum, that stores tungstate in preparation for its use in enzymes involved in SCFA generation. This revealed several families of tungstate binding proteins that are also involved in tungstate transport and tungstate-dependent regulation and are widely distributed in the human gut microbiome. Elucidating how tungsten is stored and transported in the human gut microbes contributes to our understanding of the human gut microbiome and its impact on human health.

人类肠道微生物群中普遍存在含钨的酶,而不是无处不在的类似元素钼,特别是在有助于整体肠道健康的微生物中。柠檬酸杆菌(Eubacterium limosum)是一种主要的人类肠道微生物,它利用乳酸生产有益的短链脂肪酸(SCFAs),其中涉及到钨酶。在这里,我们描述了一种钨储存蛋白--E. limosum Tub的特征。Tub 对钨酸盐的亲和力达到亚纳摩尔级,并含有一个首次在钼酸盐储存蛋白中发现的单 TOBE 结构域。晶体结构显示,Tub 组装成一个由三聚二聚体组成的六聚体,能够在位于亚基间界面的两个不同结合位点上结合八个钨酸盐氧阴离子。钨酸盐饱和的 Tub 表现出异常高的热稳定性和化学稳定性。葡萄糖生长的利莫索酵母会在 Tub 中积累钨,并含有两种钨酶,即 WOR1 和 FDH,它们分别氧化醛和甲酸。乳酸生长的细胞含有高浓度的这两种钨stoenzymes,其中 WOR1 和 FDH 参与将乳酸转化为 SCFAs。葡萄糖生长的细胞似乎在 Tub 中积累了钨酸盐,为在人体肠道中获得乳酸盐做准备。Tub和其他含TOBE的蛋白质广泛存在于人类肠道微生物群中,基因共现分析预测,参与钨酸盐储存的含TOBE的蛋白质数量与结合钼酸盐的蛋白质数量相当。对E.limosum的研究结果是了解人类肠道微生物内钨酶储存钨机制的重要一步。重要意义钨代谢被发现在人类肠道微生物组中很普遍,它参与食物和抗菌醛的解毒,以及有益SCFAs的产生。在这项研究中,我们描述了人类肠道微生物--柠檬酸杆菌(Eubacterium limosum)--中的一种蛋白质的特征,这种蛋白质能储存钨酸盐,以备在参与产生 SCFA 的酶中使用。这揭示了几个钨酸盐结合蛋白家族,它们也参与钨酸盐转运和钨酸盐依赖性调节,并广泛分布于人类肠道微生物群中。阐明钨如何在人体肠道微生物中储存和运输有助于我们了解人体肠道微生物组及其对人体健康的影响。
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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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