Department of Chemistry, Texas A&M University, College Station Texas, 77843, United States.
Department of Chemistry, Texas A&M University, College Station Texas, 77843, United States.
Curr Opin Chem Biol. 2018 Dec;47:134-141. doi: 10.1016/j.cbpa.2018.09.015. Epub 2018 Nov 15.
The recently discovered futalosine-dependent menaquinone biosynthesis pathway employs radical chemistry for the naphthoquinol core assembly. Mechanistic studies on this pathway have resulted in the discovery of novel reaction motifs. MqnA is the first example of a chorismate dehydratase. MqnE is the first example of a radical SAM enzyme that catalyzes the addition of the 5'-deoxyadenosyl radical to the substrate double bond rather than hydrogen atom abstraction. Both MqnE and MqnC reaction sequences involve radical additions to a benzene ring followed by formation of an aryl radical anion intermediate. The enzymology of the tailoring reactions after dihydroxynaphthoic acid formation remains to be elucidated. Since the futalosine-dependent menaquinone biosynthesis pathway is absent in humans, mechanistic studies on this pathway may promote the development of new antibiotics.
最近发现的依赖 futalosine 的menaquinone 生物合成途径采用自由基化学方法来组装萘醌醇核心。对该途径的机制研究导致了新反应基序的发现。MqnA 是第一个分支酸脱水酶的例子。MqnE 是第一个催化 5'-脱氧腺苷自由基与底物双键而不是氢原子提取加成的 radical SAM 酶的例子。MqnE 和 MqnC 的反应序列都涉及到对苯环的自由基加成，然后形成芳基自由基阴离子中间体。二羟萘酸形成后的修饰反应的酶学仍有待阐明。由于 futalosine 依赖的menaquinone 生物合成途径在人类中不存在，因此对该途径的机制研究可能会促进新型抗生素的开发。
