Department of Biochemistry, Okayama University of Science, Okayama City, Okayama 700-0005, Japan.
Department of Biochemistry, Okayama University of Science, Okayama City, Okayama 700-0005, Japan.
Bioorg Med Chem Lett. 2019 Sep 1;29(17):2487-2492. doi: 10.1016/j.bmcl.2019.07.018. Epub 2019 Jul 9.
HTL/KAI2, a member of the α/β-fold hydrolase superfamily, is known to be a receptor-like protein of lactone compounds and that triggers seed germination of Arabidopsis. However, the endogenous ligand and physiological roles of HTL/KAI2 have remained unclear. To understand the mechanism underlying seed germination involved in HTL/KAI2 signaling, it is necessary to identify the endogenous ligand of HTL/KAI2. To date, even a biosynthetic mutant of the ligand has not yet been isolated. Because exogenous agonistic chemicals can only be purchased in small amounts at high prices, the limited supply of those chemicals has hampered any large-scale experiments, such as mutant screening. Therefore, easily synthesized and scalable artificial agonist would remove the limitation of the chemical supply and contribute to the identification of the endogenous ligand of HTL/KAI2 and/or the biosynthetic mutants. In this study, we demonstrated that designed chemicals with a phenoxyfuranone scaffold potently stimulated seed germination via HTL/KAI2 in Arabidopsis. As a result of screening of these chemicals, we selected a representative compound with convincing selectivity. Here in, we provide a new promising synthetic agonist of HTL/KAI2.
HTL/KAI2 是 α/β 折叠水解酶超家族的成员，已知是内酯化合物的受体样蛋白，能够触发拟南芥种子萌发。然而，HTL/KAI2 的内源性配体和生理作用仍不清楚。为了了解涉及 HTL/KAI2 信号转导的种子萌发机制，有必要鉴定 HTL/KAI2 的内源性配体。迄今为止，甚至连配体的生物合成突变体都尚未分离出来。由于外源性激动性化学物质只能以高价少量购买，因此这些化学物质的有限供应阻碍了任何大规模实验，例如突变体筛选。因此，易于合成和可扩展的人工激动剂将消除化学物质供应的限制，并有助于鉴定 HTL/KAI2 的内源性配体和/或生物合成突变体。在这项研究中，我们证明了具有苯氧基呋喃酮支架的设计化学物质能够通过 HTL/KAI2 在拟南芥中强烈刺激种子萌发。作为对这些化学物质进行筛选的结果，我们选择了一种具有令人信服选择性的代表性化合物。在这里，我们提供了一种新的有前途的 HTL/KAI2 合成激动剂。
