Society Awards 2014
ストリゴラクトン機能を制御する化合物の創製研究
2014 年 39 巻 3 号 p. 170-171
詳細
2014 年 39 巻 3 号 p. 170-171
Strigolactones (SLs) are plant hormones that regulate various developmental phenomena over the plant life cycle. In this study, we screened the chemical library of triazole derivatives to find SL biosynthetic inhibitors and developed novel SL biosynthetic inhibitors. One of the SL biosynthetic inhibitors, TIS108, was particularly potent and reduced SL levels in planta and induced SL biosynthetic mutant-like morphology in Arabidopsis.
SLs are carotenoid-derived plant hormones with various biological functions, such as promoting shoot branching, root development, secondary growth, and leaf senescence. In addition, SLs are rhizosphere-signaling molecules that regulate germination of the root parasitic weeds Striga and Orobanche and induce hyphal branching in arbuscular mycorrhizal fungi. Genetic analysis of several mutants with aberrant branching patterns in Arabidopsis, rice, pea, and petunia plants revealed certain SL biosynthesis and signaling factors. To date, at least four enzymes, one carotenoid isomerase (D27); two carotenoid cleavage dioxygenases, CCD7 (MAX3, D17, DAD3 and RMS5) and CCD8 (MAX4, D10, DAD1 and RMS1); and one cytochrome P450 (MAX1) have been shown to be involved in SL biosynthesis (Fig. 1). D14/DAD2 and MAX2/D3/RMS4 encode alpha/beta hydrolase, the putative SL receptor, and an F-box protein, respectively. Recently, D53, which interacts with D14 protein in the presence of SLs, was reported to be a repressor of SL signaling.
Function regulators of plant hormones can be used not only as agrochemicals in the field but also as chemical tools for understanding plant biological processes. Recently, various chemicals have been developed and have contributed to revealing the hormone receptors and signaling factors in these processes. For example, one of the abscisic acid receptors, PYRABACTIN RESISTANCE1 (PYR1), was found via a mutant screening using pyrabactin, an agonist of abscisic acid. Standard genetic screening using brassinosteroid biosynthesis inhibitors to identify mutants that confer resistance to brassinosteroid inhibitors also succeeded in isolating some brassinosteroid signaling factors, such as BZR1, BES1, and BPG2. In this review, we introduce the SL biosynthetic inhibitors found by our group.
1H-1,2,4-triazole derivatives such as uniconazole-P and paclobutrazol inhibit various cytochrome P450s by binding to the heme iron in cytochrome P450. Specifically, uniconazole-P, which is known as a plant growth regulator, inhibits the P450s that are involved in gibberellin, brassinosteroid, and cytokinin biosynthesis as well as abscisic acid metabolism. It is known that some CYP711 family genes are involved in the SL biosynthetic pathway. To develop novel SL biosynthetic inhibitors, we attempted to screen a chemical library of triazole derivatives constructed in our laboratory. In rice hydroponic culture systems, outgrowth of the first and second tiller buds in 2-week-old SL-deficient mutants, such as d10 and d17, is observed, but this outgrowth does not occur in the wild type (Fig. 2). Thus, we screened for chemicals that induce first and second tiller bud outgrowth as candidates for SL biosynthetic inhibitors. Although no chemicals inducing first tiller bud outgrowth were found, we identified some chemicals inducing second tiller bud outgrowth. One of these, TIS13, strongly induced second tiller bud outgrowth and suppressed the level of 2′-epi-5-deoxystrigol (epi-5DS), one of the major SLs in rice. In addition, co-application of GR24, a synthetic SL, with TIS13 recovered second tiller bud dormancy. These results strongly indicate that TIS13 is an SL biosynthetic inhibitor. However, TIS13-treated plants showed the dwarf phenotype, which is not rescued by GR24 application.
To develop specific SL biosynthetic inhibitors, we synthesized some TIS13 derivatives. The ability of these chemicals to inhibit SL biosynthesis and cause dwarfism was determined by analyzing the level of epi-5DS in root exudates by LC-MS/MS and measuring the length of the second leaf sheath in rice, respectively. As a result, we found a novel SL biosynthesis inhibitor, TIS108. TIS108 reduced the level of SLs in various plant species such as rice, sorghum, and Lotus japonicus, and TIS108-treated rice did not show the dwarf phenotype. The root exudates of TIS108-treated rice seedlings also contained fewer germination-stimulating factors than those of control plants. These results indicate that TIS108 could potentially be applied to reduce the infection of root parasitic weeds. Furthermore, treatment with TIS108 induced SL-deficient mutant-like phenotypes, such as increasing the number of branches and repressing root hair elongation. Co-application of GR24 with TIS108 canceled the chemically induced phenotypes. Quantitative RT-PCR analysis revealed that SL-response genes were regulated in TIS108-treated plants. These results indicate that TIS108 is a specific SL biosynthesis inhibitor.
To explore the other leading candidate chemicals for SL biosynthesis inhibitors, we investigated the inhibitory potency of several triazole and imidazole derivatives that are on the market. We found that tebuconazole is the new leading chemical for an SL biosynthetic inhibitor. Tebuconazole reduced the level of epi-5DS in root exudates more effectively than TIS13. Structure–activity relationship studies of tebuconazole derivatives produced more effective inhibitors.
In this study, we developed some SL biosynthesis inhibitors. TIS108 was the most potent of these. We expect that these inhibitors will be useful for the investigation of SL function in various plant species and for unveiling novel SL signaling factors. However, there remains a great deal of room for the development of more potent SL biosynthesis inhibitors. Further structure-activity relationship studies on TIS108 and other SL biosynthesis inhibitors can provide more specific and potent inhibitors to regulate SL function.
