Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF.
Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF.
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DOI：
10.1038/s41467-021-27636-3
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Abe I
中科院分区：
文献类型：
--
作者：
Tao H;Mori T;Chen H;Lyu S;Nonoyama A;Lee S;Abe I
非血红素铁和α-酮戊二酸依赖性（Fe/αKG）加氧酶催化多种氧化生物转化。Fe/αKG加氧酶具有催化活性高、催化活性强等优点，在生物催化领域的应用受到广泛关注。在这里，我们报告的生物化学和结构特征的异常混杂和催化通用的Fe/αKG加氧酶SptF，参与真菌meroterpenoid emervaridones的生物合成。体外分析表明，SptF催化几个连续的氧化反应，包括羟基化，去饱和，环氧化和骨架重排。SptF对各种meroterpenoids表现出非常广泛的底物特异性，并从terretonins有效地产生独特的环丙烷环稠合的5/3/5/5/6/6和5/3/6/6支架。此外，SptF还羟基化类固醇，包括雄酮，睾酮和孕酮，具有不同的区域特异性。SptF的晶体学和基于结构的突变研究揭示了酶反应的分子基础，并表明环区的可塑性导致了显着的底物混杂。SptF是一种很有前途的生物催化剂，在氧化反应中具有很大的应用潜力。非血红素铁和α-酮戊二酸依赖性加氧酶（Fe/αKG）因其灵活性和高效性而成为生物催化剂的研究热点。在这里，作者展示了多功能Fe/αKG加氧酶SptF的生化和结构特征，该酶参与了真菌部分萜类emervaridones的生物合成。
Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases catalyze various oxidative biotransformations. Due to their catalytic flexibility and high efficiency, Fe/αKG oxygenases have attracted keen attention for their application as biocatalysts. Here, we report the biochemical and structural characterizations of the unusually promiscuous and catalytically versatile Fe/αKG oxygenase SptF, involved in the biosynthesis of fungal meroterpenoid emervaridones. The in vitro analysis revealed that SptF catalyzes several continuous oxidation reactions, including hydroxylation, desaturation, epoxidation, and skeletal rearrangement. SptF exhibits extremely broad substrate specificity toward various meroterpenoids, and efficiently produced unique cyclopropane-ring-fused 5/3/5/5/6/6 and 5/3/6/6/6 scaffolds from terretonins. Moreover, SptF also hydroxylates steroids, including androsterone, testosterone, and progesterone, with different regiospecificities. Crystallographic and structure-based mutagenesis studies of SptF revealed the molecular basis of the enzyme reactions, and suggested that the malleability of the loop region contributes to the remarkable substrate promiscuity. SptF exhibits great potential as a promising biocatalyst for oxidation reactions. Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases have attracted attention for their application as biocatalysts due to their flexibility and high efficiency. Here, the authors show the biochemical and structural characterizations of the versatile Fe/αKG oxygenase SptF, involved in the biosynthesis of fungal meroterpenoid emervaridones.
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DOI：
10.1002/anie.202017086
发表时间：
2021-04-06
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Einsiedler M;Jamieson CS;Maskeri MA;Houk KN;Gulder TAM
通讯作者：
Gulder TAM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
非血红素铁/α-KG 依赖性脱羧酶 (ScoE) 催化异腈形成的机理研究
影响因子：
12.9
作者：
Li, Hong;Liu, Yongjun
通讯作者：
Liu, Yongjun
影响因子：
--
作者：
Havemann, Judith;Vogel, Dominik;Keller, Ulrich
通讯作者：
Keller, Ulrich
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH