美国宾夕法尼亚州立大学Carsten Krebs团队报道了铁加氧酶从2-氧戊二酸中切除乙烯的杂交自由基-极性途径。相关研究成果于2021年9月24日发表于国际顶尖学术期刊《科学》。

微生物乙烯形成酶（EFE）将普遍存在的初级代谢物2-酮戊二酸（2OG）的C3–C4片段转化为其同名的烯烃产物。该反应与相关酶促进的2OG简单脱羧生成琥珀酸存在明显差异，并引发了不同的机理假设。

研究人员表明，EFE从（3S，4R）-[²H₂]-2OG生成立体化学无规（顺式和反式相等）1,2-[²H₂]-乙烯，将O₂中的氧添加到C1衍生的（bi）碳酸盐上，并通过与2OG或酶的修饰转化为ω-羟基化单酸产物。以上结果揭示了一种不同寻常的涉及铁（II）-配位酰基过氧碳酸酯和烷基碳酸酯中间体的自由基-极性杂化机制。

该机制解释了EFE如何访问高能羧基以启动其裂解级联反应，并暗示了可能有待发现和开发的2OG依赖酶的能力。

附：英文原文

Title: Hybrid radical-polar pathway for excision of ethylene from 2-oxoglutarate by an iron oxygenase

Author: Rachelle A. Copeland, Shengbin Zhou, Irene Schaperdoth, Tokufu Kent C. Shoda, J. Martin BollingerJr., Carsten Krebs

Issue&Volume: 2021-09-24

Abstract: Microbial ethylene-forming enzyme (EFE) converts the C3–C4 fragment of the ubiquitous primary metabolite 2-oxoglutarate (2OG) to its namesake alkene product. This reaction is very different from the simple decarboxylation of 2OG to succinate promoted by related enzymes and has inspired disparate mechanistic hypotheses. We show that EFE produces stereochemically random (equal cis and trans) 1,2-[2H2]-ethylene from (3S,4R)-[2H2]-2OG, appends an oxygen from O2 on the C1-derived (bi)carbonate, and can be diverted to ω-hydroxylated monoacid products by modifications to 2OG or the enzyme. These results implicate an unusual radical-polar hybrid mechanism involving iron(II)-coordinated acylperoxycarbonate and alkylcarbonate intermediates. The mechanism explains how EFE accesses a high-energy carboxyl radical to initiate its fragmentation cascade, and it hints at capabilities of 2OG-dependent enzymes that may await discovery and exploitation.

DOI: abj4290

Source: https://www.science.org/doi/10.1126/science.abj4290