Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Am Chem Soc. 2021 Nov 10;143(44):18413-18418. doi: 10.1021/jacs.1c10201. Epub 2021 Oct 28.
Belactosins and hormaomycins are peptide natural products containing 3-(2-aminocyclopropyl)alanine and 3-(2-nitrocyclopropyl)alanine residues, respectively, with opposite stereoconfigurations of the cyclopropane ring. Herein we demonstrate that the heme oxygenase-like enzymes BelK and HrmI catalyze the N-oxygenation of l-lysine to generate 6-nitronorleucine. The nonheme iron enzymes BelL and HrmJ then cyclize the nitroalkane moiety to the nitrocyclopropane ring with the desired stereochemistry found in the corresponding natural products. We also show that both cyclopropanases remove the 4--H of 6-nitronorleucine during the cyclization, establishing the inversion and retention of the configuration at C4 during the BelL and HrmJ reactions, respectively. This study reveals the unique strategy for stereocontrolled cyclopropane synthesis in nature.
贝拉妥辛类和霍马霉素类是分别含有 3-(2-氨基环丙基)丙氨酸和 3-(2-硝基环丙基)丙氨酸残基的肽类天然产物，其环丙烷环的立体构型相反。本文证明血红素加氧酶样酶 BelK 和 HrmI 催化 l-赖氨酸的 N-氧化生成 6-硝基正亮氨酸。然后，非血红素铁酶 BelL 和 HrmJ 将硝基烷部分环化成具有相应天然产物中发现的所需立体化学的硝基环丙烷环。我们还表明，两种环丙烷酶在环化过程中去除 6-硝基正亮氨酸的 4--H，从而分别在 BelL 和 HrmJ 反应中建立 C4 构型的反转和保留。这项研究揭示了自然界中环丙烷立体控制合成的独特策略。
