Institute of Biological Chemistry, Academia Sinica, Taipei, 115, Taiwan R.O.C.
Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan R.O.C.
Angew Chem Int Ed Engl. 2024 May 13;63(20):e202401324. doi: 10.1002/anie.202401324. Epub 2024 Apr 9.
We report the discovery and biosynthesis of new piperazine alkaloids-arizonamides, and their derived compounds-arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non-heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3-alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.
我们报告了新的哌嗪生物碱——阿瑞佐酰胺及其衍生化合物——阿瑞佐利定的发现和生物合成，它们分别具有杂双环和螺环异喹啉酮骨架。它们的生物合成途径涉及两个关键的非血红素铁酶，ParF 和 ParG，用于核心骨架的构建。ParF 具有双重功能，促进 helvamide 的 2,3-烯烃形成，作为 ParG 的底物，并进行哌嗪的氧化裂解。值得注意的是，ParG 在多种氧化反应中表现出催化多样性，包括环化和环重建。一个关键的氨基酸残基 Phe67 被表征为通过 ParG 控制受限的阿瑞佐酰胺 B 骨架的形成。
