The MttB superfamily member MtyB from the human gut symbiont Eubacterium limosum is a cobalamin-dependent γ-butyrobetaine methyltransferase.
The MttB superfamily member MtyB from the human gut symbiont Eubacterium limosum is a cobalamin-dependent γ-butyrobetaine methyltransferase.
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DOI：
10.1016/j.jbc.2021.101327
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Krzycki JA
中科院分区：
文献类型：
--
作者：
Ellenbogen JB;Jiang R;Kountz DJ;Zhang L;Krzycki JA
通过肠道微生物酶从季胺如l-肉毒碱或γ-丁基甜菜碱（4-（三甲基铵基）丁酸酯）产生三甲胺（TMA）与心脏病有关。这已经引起了对可能改善净TMA产生的肠道微生物组的酶的兴趣，例如MttB蛋白超家族的成员，其可以使TMA脱甲基（例如，MttB）或L-肉毒碱（例如，MtcB）。在这里，我们表明，人类肠道产乙酸真杆菌limosum去甲基化γ-丁基甜菜碱，并产生MtyB，以前未表征的MttB超家族成员催化γ-丁基甜菜碱的去甲基化。对在γ-丁酰甜菜碱或dl-乳酸盐上生长的E. limosum进行蛋白质组学分析，以鉴定生长底物的分解代谢去甲基化的潜在候选蛋白质。在γ-丁酰甜菜碱生长的细胞中，三种蛋白质的丰度显著升高：MtyB、MtqC（类咕啉结合蛋白）和MtqA（类咕啉：四氢叶酸甲基转移酶）。这些蛋白质一起充当γ-丁酰甜菜碱：四氢叶酸甲基转移酶系统，形成产乙酸的关键中间体。重组MtyB充当γ-丁酰甜菜碱：MtqC甲基转移酶，但不能甲基化游离钴胺素辅因子。MtyB与MtcB（肉毒碱甲基转移酶）非常相似，但在生长于肉毒碱上的细胞中检测不到，在生长于γ-丁酰甜菜碱下的细胞中也检测不到。两种季胺都是两种酶的底物，但动力学分析显示，与MtcB相比，MtyB对γ-丁酰甜菜碱具有较低的表观Km和较高的表观Vmax，这为γ-丁酰甜菜碱生长的细胞中的MtyB丰度提供了依据。由于TMA很容易从γ-丁基甜菜碱产生，具有MtyB样蛋白的生物体可以通过前体竞争提供降低TMA和致动脉粥样硬化的TMA-N-氧化物水平的方法。
The production of trimethylamine (TMA) from quaternary amines such as l-carnitine or γ-butyrobetaine (4-(trimethylammonio)butanoate) by gut microbial enzymes has been linked to heart disease. This has led to interest in enzymes of the gut microbiome that might ameliorate net TMA production, such as members of the MttB superfamily of proteins, which can demethylate TMA (e.g., MttB) or l-carnitine (e.g., MtcB). Here, we show that the human gut acetogen Eubacterium limosum demethylates γ-butyrobetaine and produces MtyB, a previously uncharacterized MttB superfamily member catalyzing the demethylation of γ-butyrobetaine. Proteomic analyses of E. limosum grown on either γ-butyrobetaine or dl-lactate were employed to identify candidate proteins underlying catabolic demethylation of the growth substrate. Three proteins were significantly elevated in abundance in γ-butyrobetaine-grown cells: MtyB, MtqC (a corrinoid-binding protein), and MtqA (a corrinoid:tetrahydrofolate methyltransferase). Together, these proteins act as a γ-butyrobetaine:tetrahydrofolate methyltransferase system, forming a key intermediate of acetogenesis. Recombinant MtyB acts as a γ-butyrobetaine:MtqC methyltransferase but cannot methylate free cobalamin cofactor. MtyB is very similar to MtcB, the carnitine methyltransferase, but neither was detectable in cells grown on carnitine nor was detectable in cells grown with γ-butyrobetaine. Both quaternary amines are substrates for either enzyme, but kinetic analysis revealed that, in comparison to MtcB, MtyB has a lower apparent Km for γ-butyrobetaine and higher apparent Vmax, providing a rationale for MtyB abundance in γ-butyrobetaine-grown cells. As TMA is readily produced from γ-butyrobetaine, organisms with MtyB-like proteins may provide a means to lower levels of TMA and proatherogenic TMA-N-oxide via precursor competition.
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影响因子：
3.7
作者：
Biagi E;Nylund L;Candela M;Ostan R;Bucci L;Pini E;Nikkïla J;Monti D;Satokari R;Franceschi C;Brigidi P;De Vos W
通讯作者：
De Vos W
影响因子：
11.2
作者：
Bae S;Ulrich CM;Neuhouser ML;Malysheva O;Bailey LB;Xiao L;Brown EC;Cushing-Haugen KL;Zheng Y;Cheng TY;Miller JW;Green R;Lane DS;Beresford SA;Caudill MA
通讯作者：
Caudill MA
DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
影响因子：
12.2
作者：
Brugère JF;Borrel G;Gaci N;Tottey W;O'Toole PW;Malpuech-Brugère C
通讯作者：
Malpuech-Brugère C
影响因子：
4.8
作者：
Israr, Muhammad Zubair;Bernieh, Dennis;Suzuki, Toru
通讯作者：
Suzuki, Toru