Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
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DOI：
10.1073/pnas.1215689109
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发表时间：
2012-12-26
影响因子：
11.1
通讯作者：
Balskus, Emily P.
中科院分区：
文献类型：
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作者：
Craciun, Smaranda;Balskus, Emily P.
胆碱和三甲胺（TMA）是在所有生命王国的生物过程中发挥核心作用的小分子。这些无处不在的代谢物通过单一的生化转化，即厌氧微生物将胆碱转化为TMA而联系在一起。这种代谢活动，有助于甲烷生成和人类疾病，已经知道了一个多世纪，但一直回避遗传和生物化学表征。我们已经确定了一个基因簇负责厌氧胆碱降解的硫酸盐还原菌的基因组内，并验证了其功能，同时使用基因敲除策略和异源表达在大肠杆菌。生物信息学和电子顺磁共振（EPR）光谱揭示了一个C-N键裂解甘氨酰自由基酶在TMA生产中的参与，这是前所未有的化学为这个酶家族。我们的发现提供了识别许多细菌基因组中胆碱利用簇所需的预测能力，强调了这种代谢活动在人类微生物群和环境中的重要性和普遍性。
Choline and trimethylamine (TMA) are small molecules that play central roles in biological processes throughout all kingdoms of life. These ubiquitous metabolites are linked through a single biochemical transformation, the conversion of choline to TMA by anaerobic microorganisms. This metabolic activity, which contributes to methanogenesis and human disease, has been known for over a century but has eluded genetic and biochemical characterization. We have identified a gene cluster responsible for anaerobic choline degradation within the genome of a sulfate-reducing bacterium and verified its function using both a genetic knockout strategy and heterologous expression in Escherichia coli. Bioinformatics and electron paramagnetic resonance (EPR) spectroscopy revealed the involvement of a C-N bond cleaving glycyl radical enzyme in TMA production, which is unprecedented chemistry for this enzyme family. Our discovery provides the predictive capabilities needed to identify choline utilization clusters in numerous bacterial genomes, underscoring the importance and prevalence of this metabolic activity within the human microbiota and the environment.