Identification of Cyclopropane Formation in the Biosyntheses of Hormaomycins and Belactosins: Sequential Nitration and Cyclopropanation by Metalloenzymes.
Identification of Cyclopropane Formation in the Biosyntheses of Hormaomycins and Belactosins: Sequential Nitration and Cyclopropanation by Metalloenzymes.
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DOI：
10.1002/anie.202113189
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发表时间：
2022-02-07
期刊：
影响因子：
--
通讯作者：
Ogasawara Y
中科院分区：
文献类型：
--
作者：
Li X;Shimaya R;Dairi T;Chang WC;Ogasawara Y
激素和belactosins是肽类天然产物，含有不寻常的环丙烷部分。生物信息学分析表明，hrmI/belK和hrmJ/belL两个保守基因是催化环丙烷化反应的潜在候选基因。利用体内和体外实验，建立了HrmI/BelK和HrmJ/BelL的功能。HrmI和BelK是血红素加氧酶样双核铁酶，催化L-赖氨酸的ε-氨基氧化生成1 -6-硝基正亮氨酸。随后，铁和α-酮戊二酸依赖性加氧酶HrmJ和BelL通过C4-C6键安装有效地将1 -6-硝基正亮氨酸转化为3-（反式-2-硝基环丙基）丙氨酸。这些发现揭示了环丙烷环构建的新途径，并揭示了天然产物生物合成中涉及金属酶的新化学。充分阐明了荷马霉素和贝拉克菌素中氨基/硝基环丙基丙氨酸部分的生物合成途径。该途径涉及血红素加氧酶样双核铁酶（HrmI/BelK）对L-赖氨酸的ε-氨基的六电子氧化以及铁和α-酮戊二酸依赖性加氧酶（HrmJ/BelL）的C-C键形成。这是Fe/α-KG加氧酶催化环丙烷形成的第一个例子。
Hormaomycins and belactosins are peptide natural products that contain unusual cyclopropane moieties. Bioinformatics analysis of the corresponding biosynthetic gene clusters showed that two conserved genes, hrmI/belK and hrmJ/belL, were potential candidates for catalyzing cyclopropanation. Using in vivo and in vitro assays, the functions of HrmI/BelK and HrmJ/BelL were established. HrmI and BelK, which are heme oxygenase-like dinuclear iron enzymes, catalyze oxidation of the ε-amino group of l-lysine to afford l-6-nitronorleucine. Subsequently, HrmJ and BelL, which are iron- and α-ketoglutarate-dependent oxygenases, effectively convert l-6-nitronorleucine into 3-(trans-2-nitrocyclopropyl)alanine through C4–C6 bond installation. These observations disclose a novel pathway of cyclopropane ring construction and exemplify the new chemistry involving metalloenzymes in natural product biosynthesis. The biosynthetic pathway of amino/nitro-cyclopropylalanine moieties in hormaomycin and belactosin was fully elucidated. The pathway involves six-electron oxidation of the ε-amino group of l-lysine by heme oxygenase-like dinuclear iron enzymes (HrmI/BelK) and C–C bond formation by iron- and α-ketoglutarate-dependent oxygenases (HrmJ/BelL). This is the first example of Fe/α-KG oxygenase-catalyzed cyclopropane formation.
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影响因子：
12.9
作者：
Chen, Tzu-Yu;Xue, Shan;Chang, Wei-chen
通讯作者：
Chang, Wei-chen
影响因子：
15
作者：
He, Hai-Yan;Henderson, Alyssa C.;Ryan, Katherine S.
通讯作者：
Ryan, Katherine S.
DOI：
10.1126/science.aac7202
发表时间：
2015-09-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lau W;Sattely ES
通讯作者：
Sattely ES
影响因子：
13.8
作者：
Herr CQ;Hausinger RP
通讯作者：
Hausinger RP
天然产物生物合成中α-酮戊二酸依赖性单核非血红素铁酶的最新实例。
影响因子：
11.9
作者：
Gao SS;Naowarojna N;Cheng R;Liu X;Liu P
通讯作者：
Liu P