Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase.
Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase.
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DOI：
10.1038/s42004-021-00545-8
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发表时间：
2021-07-16
影响因子：
5.9
通讯作者：
Ito, Sohei
中科院分区：
文献类型：
--
作者：
Motoyama, Tomoharu;Nakano, Shogo;Hasebe, Fumihito;Miyata, Ryo;Kumazawa, Shigenori;Miyoshi, Noriyuki;Ito, Sohei
吡嗪通常由氨基酸和糖在化学反应（例如美拉德反应）中形成。在这项研究中，我们证明可以通过简单的细菌操纵子从 L-Thr 生产 3-乙基-2,5-二甲基吡嗪。我们得出结论，EDMP 是由 L-Thr 通过两分子氨基丙酮和一分子乙醛的缩合反应以化学酶法合成的。氨基丙酮由 L-苏氨酸 3-脱氢酶使用 L-Thr 作为底物通过 2-氨基-3-酮丁酸提供。当 CoA 浓度较低时，乙醛由具有苏氨酸醛缩酶活性的 2-氨基-3-酮丁酸 CoA 连接酶从 L-Thr 提供。考虑到EDMP的产率，反应中间体在一定时间内稳定，适度的反应温度对于EDMP的合成很重要。当这些酶从L-Thr提供前体时，EDMP的产率增加至20.2%。此外，我们证明该反应可用于合成各种烷基吡嗪。苏氨酸是二甲基吡嗪衍生物的生物合成前体，但其发生的途径尚未完全确定。此处，L-苏氨酸-3-脱氢酶和 2-氨基-3-酮丁酸 CoA 连接酶一起被证明可将 L-苏氨酸转化为二甲基吡嗪衍生物，作为甘氨酸代谢的副产物。
Pyrazines are typically formed from amino acids and sugars in chemical reactions such as the Maillard reaction. In this study, we demonstrate that 3-ethyl-2,5-dimethylpyrazine can be produced from L-Thr by a simple bacterial operon. We conclude that EDMP is synthesized chemoenzymatically from L-Thr via the condensation reaction of two molecules of aminoacetone and one molecule of acetaldehyde. Aminoacetone is supplied by L-threonine 3-dehydrogenase using L-Thr as a substrate via 2-amino-3-ketobutyrate. Acetaldehyde is supplied by 2-amino-3-ketobutyrate CoA ligase bearing threonine aldolase activity from L-Thr when CoA was at low concentrations. Considering the rate of EDMP production, the reaction intermediate is stable for a certain time, and moderate reaction temperature is important for the synthesis of EDMP. When the precursor was supplied from L-Thr by these enzymes, the yield of EDMP was increased up to 20.2%. Furthermore, we demonstrate that this reaction is useful for synthesizing various alkylpyrazines. Threonine is a biosynthetic precursor to dimethylpyrazine derivatives, but the pathway by which this occurs is not fully established. Here l-throenine-3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase together are shown to convert l-threonine to dimethylpyrazine derivatives as a byproduct of glycine metabolism.
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影响因子：
4.4
作者：
Larroche, C;Besson, I;Gros, JB
通讯作者：
Gros, JB
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
4.1
作者：
Hamilton, CJ;Saravanamuthu, A;Fairlamb, AH
通讯作者：
Fairlamb, AH
影响因子：
3.2
作者：
Kazuoka, T;Takigawa, S;Soda, K
通讯作者：
Soda, K
影响因子：
4
作者：
Kashiwayanagi M;Miyazono S;Osada K
通讯作者：
Osada K