Institute of Biochemistry and Molecular Biology, College of Medicine, National (Taiwan) University, Taipei, 100, Taiwan.
Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Angew Chem Int Ed Engl. 2018 Feb 12;57(7):1831-1835. doi: 10.1002/anie.201710567. Epub 2018 Jan 16.
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 -oxo species and the subsequent formation of a carbocation or a hydroxylated intermediate is preferred during AsqJ-catalyzed desaturation.
AsqJ 是一种铁(II)和 2-氧代戊二酸依赖性酶，存在于绿麦角碱型生物碱生物合成途径中，催化顺序去饱和和环氧化反应生成环杷明。报道了 AsqJ 与环杷肽及其 C3 差向异构体结合的晶体结构。同时，进行了详细的机制研究以破译去饱和机制。这些发现表明，在 AsqJ 催化的去饱和过程中，优先选择涉及通过短寿命 Fe-氧物种在底物的 C10 位置上进行氢原子提取，随后形成碳正离子或羟基化中间体的途径。
