Miyazaki Sho, Tomita Kenji, Yamane Hisakazu, Kobayashi Masatomo, Asami Tadao, Nakajima Masatoshi
Department of Applied Biological Chemistry, The University of Tokyo, Tokyo 113-8657, Japan.
Division of Integrated Science and Engineering, Graduate School of Science and Engineering, Teikyo University, Utsunomiya 320-8551, Japan.
Bioorg Med Chem Lett. 2018 Aug 1;28(14):2465-2470. doi: 10.1016/j.bmcl.2018.06.005. Epub 2018 Jun 5.
Helminthosporol, a natural growth regulator isolated from a fungus, stimulates hypocotyl growth and seed germination, similar to gibberellin (GA). We recently reported that helminthosporic acid (H-acid), a synthetic analog of helminthosporol, acts as an agonist of GA receptor. In this study, we showed that a H-acid analog, in which the hydroxymethyl group at the C-8 position of H-acid was converted to a keto group, acts as a selective GA receptor agonist. 1) This analog shows higher hypocotyl elongation activity in Arabidopsis than H-acid does, and induces the degradation of DELLA protein and 2) leads to the formation of the GID1-DELLA complex and 3) regulates the expression of GA-related genes. In addition, 4) its hypocotyl elongation activity was not observed in a atgid1a single mutant, and 5) this analog could promote only the interaction between specific GA receptors and DELLA proteins in vitro. Taken together, our results strongly suggest that the selectivity of the reported H-acid analog depends on the specificity of its GA receptor binding activity.
蠕孢醇是一种从真菌中分离出的天然生长调节剂，它能刺激下胚轴生长和种子萌发，作用类似于赤霉素（GA）。我们最近报道，蠕孢酸（H-酸）作为蠕孢醇的合成类似物，可作为GA受体的激动剂。在本研究中，我们发现一种H-酸类似物（其中H-酸C-8位的羟甲基被转化为酮基）可作为选择性GA受体激动剂。1）该类似物在拟南芥中显示出比H-酸更高的下胚轴伸长活性，并诱导DELLA蛋白降解；2）导致形成GID1-DELLA复合物；3）调节GA相关基因的表达。此外，4）在atgid1a单突变体中未观察到其下胚轴伸长活性；5）该类似物在体外仅能促进特定GA受体与DELLA蛋白之间的相互作用。综上所述，我们的结果有力地表明，所报道的H-酸类似物的选择性取决于其GA受体结合活性的特异性。
