Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
J Agric Food Chem. 2022 Mar 16;70(10):3109-3116. doi: 10.1021/acs.jafc.1c04984. Epub 2022 Mar 2.
Melanin is a secondary metabolite required for the infection of the rice blast fungus . Melanin biosynthesis enzymes are targets for controlling rice blast disease, and three types of commercial melanin biosynthesis inhibitors (MBIs) including MBI-R, MBI-D, and MBI-P have been developed. However, the occurrence of MBI-D-resistant strains containing scytalone dehydratase (SDH1/RSY1) with V75M mutations has been recently reported. In this study, we aimed to identify inhibitors of SDH1-V75M. We screened the RIKEN Natural Products Depository chemical library using chemical array technology and evaluated the inhibition of SDH1-V75M by candidate compounds. NPD13731 strongly inhibited the activity of wild-type and mutant SDH1. The structure-activity relationship data were used to create a more potent inhibitor , which controlled rice blast disease in rice plants infected with MBI-D-resistant . Compound , which we named melabiostin, may be used to develop fungicides for controlling rice blast infections.
黑色素是稻瘟病菌感染所必需的次生代谢物。黑色素生物合成酶是控制稻瘟病的靶标，已经开发出三种商业黑色素生物合成抑制剂（MBI），包括 MBI-R、MBI-D 和 MBI-P。然而，最近报道了含有 scytalone 脱水酶（SDH1/RSY1）V75M 突变的 MBI-D 抗性菌株的发生。在这项研究中，我们旨在鉴定 SDH1-V75M 的抑制剂。我们使用化学阵列技术筛选了 RIKEN 天然产物库化学库，并评估了候选化合物对 SDH1-V75M 的抑制作用。NPD13731 强烈抑制野生型和突变型 SDH1 的活性。结构-活性关系数据用于创建更有效的抑制剂，该抑制剂控制了感染 MBI-D 抗性的水稻植株中的稻瘟病。我们将这种化合物命名为 melabiostin，它可能被用于开发防治稻瘟病感染的杀菌剂。
