Insights into the Desaturation of Cyclopeptin and its C3 Epimer Catalyzed by a non‐Heme Iron Enzyme: Structural Characterization and Mechanism Elucidation. Issue 7 (16th January 2018)

• Record Type: Journal Article
• Authors: Liao, Hsuan‐Jen; Li, Jikun; Huang, Jhih‐Liang; Davidson, Madison; Kurnikov, Igor; Lin, Te‐Sheng; Lee, Justin L.; Kurnikova, Maria; Guo, Yisong; Chan, Nei‐Li; Chang, Wei‐chen
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 7(2018)
• Page Start: 1831
• Page End: 1835
• Publication Date: 2018-01-16
• Subjects: carbocations -- C−C bond formation -- desaturation -- enzyme mechanisms -- viridicatin; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201710567
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: AsqJ, an iron(II)‐ and 2‐oxoglutarate‐dependent enzyme found in viridicatin‐type alkaloid biosynthetic pathways, catalyzes sequential desaturation and epoxidation to produce cyclopenins. Crystal structures of AsqJ bound to cyclopeptin and its C3 epimer are reported. Meanwhile, a detailed mechanistic study was carried out to decipher the desaturation mechanism. These findings suggest that a pathway involving hydrogen atom abstraction at the C10 position of the substrate by a short‐lived Fe IV ‐oxo species and the subsequent formation of a carbocation or a hydroxylated intermediate is preferred during AsqJ‐catalyzed desaturation. Abstract : Make it a double : The mechanism of the desaturation catalyzed by AsqJ, a non‐heme iron enzyme, was elucidated using a complementary approach including probe design, X‐ray crystallography, molecular dynamics simulations, and spectroscopic characterizations. Subsequent to primary C−H bond activation, a carbocation or a hydroxylated intermediate is likely to be involved in the desaturation.