Elucidation of novel archaeal mevalonate pathways oriented to metabolic engineering application

阐明面向代谢工程应用的新型古菌甲羟戊酸途径

• 批准号: 23580111
• 负责人: HEMMI Hisashi
• 金额: $ 3.41万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23580111/
• 关键词: 酵素; 微生物; 生体分子; イソプレノイド; メバロン酸経路; アーキア; 代謝; フラビン酵素

A part of reactions in the archaeal mevalonate pathways were unidentified. Thus we performed the conversion assay of radio-labeled substrates by cell-free extract from archaea and functional characterization of archaeal homologs of known mevalonate pathway-related enzymes. As the result, we discovered the classical mevalonate pathway, which is rare in archaea, from an archaeon of genus Sulfolobus, and a novel modified pathway, which passes through 3-phosphomevalonate, from an archaeon of genus Thermoplasma.We also performed X-ray crystal structural studies on type 2 isopentenyl diphosphate isomerase and diphosphomevalonate decarboxylase from archaea of genus Sulfolobus. The obtained structures and the results of various analyses showed novel mechanisms of catalysis, regulation of activity, and thermostabilization.

古细菌甲羟戊酸途径中的一部分反应未被鉴定。因此，我们进行了转换试验的放射性标记的底物的无细胞提取物从古细菌和古细菌同系物的已知甲羟戊酸途径相关的酶的功能表征。结果，我们从硫化叶菌属古细菌中发现了古细菌中罕见的经典甲羟戊酸途径，并从热浆菌属古细菌中发现了经过3-磷酸甲羟戊酸的新型修饰途径。我们还对硫化叶菌属古细菌的2型异戊烯基二磷酸异构酶和二磷酸甲羟戊酸脱羧酶进行了X射线晶体结构研究。所获得的结构和各种分析的结果显示了新的催化机制，活性调节和热稳定性。

项目成果

好熱好酸性アーキアSulfolobus solfataricus由来ジホスホメバロン酸デカルボキシラーゼの立体構造

嗜热嗜酸古菌硫磺菌二磷酸甲羟戊酸脱羧酶的三维结构

• 发表时间: 2013
• 作者: 服部愛;海野英昭;吉村徹;邊見久
• 通讯作者: 邊見久

基質により誘導される好熱性アーキア由来タイプ2イソペンテニル二リン酸イソメラーゼの四次構造変化

嗜热古细菌 2 型异戊烯基二磷酸异构酶中底物诱导的四级结构变化

• 发表时间: 2012
• 作者: 中谷仁美;郷田秀一郎;海野英昭;長井拓也;吉村徹;邊見久
• 通讯作者: 邊見久

Archaeal phospholipid biosynthesis pathway reconstructed in E. coli

在大肠杆菌中重建古菌磷脂生物合成途径

• 发表时间: 2012
• 作者: 中谷仁美;郷田秀一郎;海野英昭;長井拓也;吉村徹;邊見久;Hisashi Hemmi
• 通讯作者: Hisashi Hemmi

Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors

• DOI: 10.1073/pnas.1115749108
• 发表时间: 2011-12-20
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Nagai, Takuya;Unno, Hideaki;Hemmi, Hisashi
• 通讯作者: Hemmi, Hisashi

A third alternative mevalonate pathway from Thermoplasma acidophilum

来自嗜酸热原体的第三种替代甲羟戊酸途径

• 发表时间: 2014
• 作者: Hisashi Hemmi;Yasuhiro Azami;Ai Hattori;Hiroshi Kawaide and Tohru Yoshimura
• 通讯作者: Hiroshi Kawaide and Tohru Yoshimura