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Expanding the Scope of Enantioselective Halohydrin Dehalogenases – Group B
Advanced Synthesis & Catalysis ( IF 4.4 ) Pub Date : 2022-06-13 , DOI: 10.1002/adsc.202200342 Emina Mehić 1 , Lucija Hok 2 , Qian Wang 3 , Irena Dokli 4 , Marina Svetec Miklenić 5 , Zvjezdana Findrik Blažević 6 , Lixia Tang 3 , Robert Vianello 2 , Maja Majerić Elenkov 2
Advanced Synthesis & Catalysis ( IF 4.4 ) Pub Date : 2022-06-13 , DOI: 10.1002/adsc.202200342 Emina Mehić 1 , Lucija Hok 2 , Qian Wang 3 , Irena Dokli 4 , Marina Svetec Miklenić 5 , Zvjezdana Findrik Blažević 6 , Lixia Tang 3 , Robert Vianello 2 , Maja Majerić Elenkov 2
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Halohydrin dehalogenases (HHDHs) possess an unnatural activity of introducing functionalities such as N3, CN, NO2 etc., into a molecule through the ring-opening reaction of epoxides. The enantioselectivity of HHDHs is substrate-dependent and not always high enough for synthetic applications. B-group of HHDHs has been neglected in the past, due to observed low enantioselectivity based on performance on a relatively limited number of substrates. Extensive screening of substrates on HheB2 from Mycobacterium sp. GP1 and HheB from Corynebacterium sp. N-1074 was performed. Several highly enantioselective reactions were discovered (E>200), with HheB showing higher enantioselectivity and activity toward larger panel of substrates compared to HheB2. Enzymes HheB and HheB2 are highly homologous; they differ by only 4 residues. By using site-directed mutagenesis, residues 120 and 125 were found to be responsible for higher enantioselectivity of HheB compared to HheB2. Computational analysis supported experiments and provided evidence that kinetic and thermodynamic parameters of reactions within HheB enzymes are crucial in determining the observed enantioselectivities. Due to remarkable activity and enantioselectivity, B-group HHDHs emerged as a catalyst of choice for the synthesis of bulky tertiary alcohols, as shown in this work.
中文翻译：
扩大对映选择性卤代醇脱卤酶的范围 – B 组
卤代醇脱卤酶(HHDHs)具有通过环氧化物的开环反应将诸如N 3、CN、NO 2等官能团引入分子中的非天然活性。HHDH 的对映选择性取决于底物，对于合成应用而言并不总是足够高。由于在相对有限数量的底物上的性能观察到的低对映选择性，HHDH 的 B 组过去一直被忽视。广泛筛选来自分枝杆菌的 HheB2 底物。来自棒状杆菌属的 GP1 和 HheB 。进行了 N-1074。发现了几个高度对映选择性的反应（E>200)，与 HheB2 相比，HheB 对更大的底物面板显示出更高的对映选择性和活性。酶 HheB 和 HheB2 高度同源；它们仅相差 4 个残基。通过使用定点诱变，发现与 HheB2 相比，残基 120 和 125 是 HheB 对映选择性更高的原因。计算分析支持实验并提供证据表明 HheB 酶内反应的动力学和热力学参数对于确定观察到的对映选择性至关重要。如本工作所示，由于显着的活性和对映选择性，B 组 HHDHs 成为合成大体积叔醇的首选催化剂。
更新日期：2022-06-13
中文翻译：
扩大对映选择性卤代醇脱卤酶的范围 – B 组
卤代醇脱卤酶(HHDHs)具有通过环氧化物的开环反应将诸如N 3、CN、NO 2等官能团引入分子中的非天然活性。HHDH 的对映选择性取决于底物，对于合成应用而言并不总是足够高。由于在相对有限数量的底物上的性能观察到的低对映选择性，HHDH 的 B 组过去一直被忽视。广泛筛选来自分枝杆菌的 HheB2 底物。来自棒状杆菌属的 GP1 和 HheB 。进行了 N-1074。发现了几个高度对映选择性的反应（E>200)，与 HheB2 相比，HheB 对更大的底物面板显示出更高的对映选择性和活性。酶 HheB 和 HheB2 高度同源；它们仅相差 4 个残基。通过使用定点诱变，发现与 HheB2 相比，残基 120 和 125 是 HheB 对映选择性更高的原因。计算分析支持实验并提供证据表明 HheB 酶内反应的动力学和热力学参数对于确定观察到的对映选择性至关重要。如本工作所示，由于显着的活性和对映选择性，B 组 HHDHs 成为合成大体积叔醇的首选催化剂。
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