Development of inhibitors for abscisic acid biosynthesis or catabolism

脱落酸生物合成或分解代谢抑制剂的开发

• 批准号: 14560088
• 负责人: ASAMI Tadao
• 金额: $ 2.24万
• 依托单位: RIKEN (The Institute of Physical and Chemical Research)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560088/
• 关键词: abscisic acid; dioxygenase; carotenoid cleaving enzyme; phaseic acid; catabolism enzyme; cytochrome P450; triazole; plant hormones; アブシシン酸; カトテノイド開裂酵素; 生合成阻害剤; リグノステイルベン; NCED; NDGA; エポキシカロテノイド; キサントキシン; 気孔

In higher plants, the ABA biosynthesis pathway involves the oxidative cleavage of 9-cis-epoxycarotenoids, which may be the key regulatory step in the pathway catalyzed by 9-cis-epoxycarotenoid dioxygenase (NCED). We developed a new inhibitor of ABA biosynthesis targeting NCED and named it abamine (abscisic acid biosynthesis inhibitor with an amine moiety). Abamine is a competitive inhibitor of NCED, with a K_i of 38.8 μM. In 0.4 M mannitol solution, which mimics the effects of osmotic stress, abamine both inhibited stomatal closure in spinach leaves, which was restored by co-application of ABA, and increased luminescence intensity in RD29B::LUC transgenic Arabidopsis. The ABA content of plants in 0.4 M mannitol was increased approximately 16-fold as compared with that of controls, whereas 50 to 100 μM abamine inhibited about 50% of this ABA accumulation in both spinach leaves and Arabidopsis. Abamine-treated Arabidopsis was more sensitive to drought stress and showed a significant decrease in drought tolerance than untreated Arabidopsis. These results suggest that abamine is a novel ABA biosynthesis inhibitor that targets the enzyme catalyzing oxidative cleavage of 9-cis-epoxycarotenoids. To test the effect of abamine on plants other than Arabidopsis, it was applied to cress plants. Abamine enhanced radicle elongation in cress seeds, which could be due to a decrease in the ABA content of abamine-treated plants. Thus, it is possible to think that abamine should enable us to elucidate the functions of ABA in cells or plants and to find new mutants involved in ABA signaling.

在高等植物中，阿坝生物合成途径涉及9-顺式-环氧类胡萝卜素的氧化裂解，这可能是9-顺式-环氧类胡萝卜素双加氧酶（NCED）催化的ABA生物合成途径中的关键调控步骤。我们开发了一种新的阿坝生物合成抑制剂，靶向NCED，并命名为abamine（脱落酸生物合成抑制剂与胺部分）。Abamine是NCED的竞争性抑制剂，Ki为38.8 μM。在0.4 M甘露醇溶液中，模拟渗透胁迫的影响，abamine既抑制菠菜叶片中的气孔关闭，这是通过共同应用的阿坝恢复，并增加发光强度在RD 29 B：：LUC转基因拟南芥。在0.4M甘露醇中，植物的阿坝含量比对照增加约16倍，而50 ~ 100 μM的阿巴明抑制了菠菜和拟南芥阿坝积累的50%左右。与未处理的拟南芥相比，Abamine处理的拟南芥对干旱胁迫更敏感，耐旱性显着降低。这些结果表明，阿巴明是一种新的阿坝生物合成抑制剂，其靶向催化9-顺式-环氧类胡萝卜素氧化裂解的酶。为了测试阿巴明对拟南芥以外的植物的作用，将其施用于水芹植物。在水芹种子，这可能是由于阿坝含量的下降，阿巴明增强胚根伸长。因此，可以认为，abamine应该使我们能够阐明阿坝在细胞或植物中的功能，并找到新的突变体参与阿坝信号转导。

项目成果

Han SY, Kamoda K, Sekimata K, Saito T, Kobayashi M, Shinozaki K, Yoshida S, Asami T: "Design and synthesis of lignostilbene-α,β-dioxygenase inhibitors"Bioorganic & Medicinal Chemistry Letters. 12. 1139-1142 (2002)

Han SY、Kamoda K、Sekimata K、Saito T、Kobayashi M、Shinozaki K、Yoshida S、Asami T：“木质芪-α,β-双加氧酶抑制剂的设计与合成”生物有机与药物化学快报 12。1139-1142（ 2002）

Han SY, Kitahata N, Sekimata K, Saito T, Kobayashi M, Nakashima K, Yamaguchi-Shinozaki K, Shinozaki K, Yoshida S, Asami T: "A novel inhibitor of 9-cis-epoxycarotenoid dioxygenase (NCED) in abscisic acid biosynthesis in higher plants."Plant Physiol. (in pr

Han SY、Kitahata N、Sekimata K、Saito T、Kobayashi M、Nakashima K、Yamaguchi-Shinozaki K、Shinozaki K、Yoshida S、Asami T：“脱落酸生物合成中的 9-顺式环氧类胡萝卜素双加氧酶 (NCED) 的新型抑制剂

Yamazaki D, Yoshida S, Asami T, Kuchitsu K: "Visualization of abscisic acid perception sites on the plasma membrane of stomatal guard cells."Plant J. 35. 129-139 (2003)

Yamazaki D、Yoshida S、Asami T、Kuchitsu K：“气孔保卫细胞质膜上脱落酸感知位点的可视化。”Plant J. 35. 129-139 (2003)

Han SY, Kamoda M, Sekimata K, Saito T, Kobayashi M, Shinozaki K, Yoshida S, Asami T: "N-Benzylideneaniline and N-benzylaniline are potent inhibitors of lignostilbene-α,β-dioxygenase, a key enzyme in oxidative cleavage of the central double bond of lignost

Han SY、Kamoda M、Sekimata K、Saito T、Kobayashi M、Shinozaki K、Yoshida S、Asami T：“N-亚苄基苯胺和 N-亚苄基苯胺是木质芪-α,β-双加氧酶（氧化裂解中的关键酶）的有效抑制剂木素中心双键

Han SY, Inoue H, Terada T, Kamoda S, Saburi Y, Sekimata K, Saito T, Kobayashi M, Shinozaki K, Yoshida S, Asami T: "Design and synthesis of lignostilbene-α,β-dioxygenase ; inhibitors."Bioorg Med Chem Lett. 12. 1139-1142 (2002)

Han SY, Inoue H, Terada T, Kamoda S, Saburi Y, Sekimata K, Saito T, Kobayashi M, Shinozaki K, Yoshida S, Asami T：“木质芪-α,β-双加氧酶的设计与合成；抑制剂。”Bioorg医学化学通讯。12。1139-1142 (2002)