Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins
Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins
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DOI：
10.1021/jacs.1c10201
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发表时间：
2021-10-28
影响因子：
15
通讯作者：
Abe, Ikuro
中科院分区：
文献类型：
--
作者：
Shimo, Shotaro;Ushimaru, Richiro;Abe, Ikuro
乳杆菌素和霍马霉素是含有3-（2-氨基环丙基）丙氨酸和3-（2-硝基环丙基）丙氨酸残基的肽天然产物，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 -氧合生成6-硝基亮氨酸。然后，非血红素铁酶BelL和hrj将硝基烷烃部分环化成硝基环丙烷环，并在相应的天然产物中发现所需的立体化学。我们还发现两种环丙酶在环化过程中去除6-硝基亮氨酸的4-proS-H，分别在BelL和hrj反应中建立了C4构型的反转和保留。本研究揭示了自然界中立体控制环丙烷合成的独特策略。
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-proS-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.