Technological watch

<i>cis</i>-Decalin-containing tetramic acids as inhibitors of insect steroidogenic glutathione <i>S</i>-transferase Noppera-bo

AbstractDecalin-containing tetramic acid is a bioactive scaffold primarily produced by filamentous fungi. The structural diversity of this group of compounds is generated by characteristic enzymes of fungal biosynthetic pathways, including polyketide synthase/nonribosomal peptide synthetase hybrid enzymes and decalin synthase, which are responsible for the construction of a linear polyenoyl tetramic acid structure and stereoselective decalin formation via the intramolecular Diels–Alder reaction, respectively. Compounds that differed only in the decalin configuration were collected from genetically engineered mutants derived from decalin-containing tetramic acid-producing fungi and used for a structure-activity relationship study. Our evaluation of biological activities, such as cytotoxicity against several cancer cell lines and antibacterial, antifungal, antimalarial, and mitochondrial inhibitory activities, demonstrated that the activity for each assay varies depending on the decalin configurations. In addition to these known biological activities, we revealed that the compounds showed inhibitory activity against the insect steroidogenic glutathione S-transferase Noppera-bo. Engineering the decalin configurations would be useful not only to find derivatives with better biological activities but also to discover overlooked biological activities.

Publication date: 31/08/2023

Author: Naoki Kato,  Kana Ebihara,  Toshihiko Nogawa,  Yushi Futamura,  Kazue Inaba,  Akiko Okano,  Harumi Aono,  Yuuta Fujikawa,  Hideshi Inoue,  Kazuhiko Mats




This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870292.