Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (−)-4′-Methoxycyclopenin Biosynthesis

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• 作者：Wei-chen Chang ; Jikun Li ; Justin L. Lee ; Andrea A. Cronican ; Yisong Guo
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：August 24, 2016
• 年：2016
• 卷：138
• 期：33
• 页码：10390-10393
• 全文大小：345K
• 年卷期：0
• ISSN：1520-5126

文摘

Mechanisms have been proposed for α-KG-dependent non-heme iron enzyme catalyzed oxygen atom insertion into an olefinic moiety in various natural products, but they have not been examined in detail. Using a combination of methods including transient kinetics, Mössbauer spectroscopy, and mass spectrometry, we demonstrate that AsqJ-catalyzed (−)-4′-methoxycyclopenin formation uses a high-spin Fe(IV)-oxo intermediate to carry out epoxidation. Furthermore, product analysis on ¹⁶O/¹⁸O isotope incorporation from the reactions using the native substrate, 4′-methoxydehydrocyclopeptin, and a mechanistic probe, dehydrocyclopeptin, reveals evidence supporting oxo↔hydroxo tautomerism of the Fe(IV)-oxo species in the non-heme iron enzyme catalysis.