Dataset Information

Highly α-position regioselective ring-opening of epoxides catalyzed by halohydrin dehalogenase from Ilumatobacter coccineus: a biocatalytic approach to 2-azido-2-aryl-1-ols.

ABSTRACT: Halohydrin dehalogenases are usually recognized as strict β-position regioselective enzymes in the nucleophile-mediated ring-opening of epoxides. Here we found the HheG from Ilumatobacter coccineus exhibited excellent α-position regioselectivity in the azide-mediated ring-opening of styrene oxide derivatives 1a-1k, producing the corresponding 2-azido-2-aryl-1-ols 2a-2k with the yields up to 96%.

SUBMITTER: An M

PROVIDER: S-EPMC9064361 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Highly α-position regioselective ring-opening of epoxides catalyzed by halohydrin dehalogenase from <i>Ilumatobacter coccineus</i>: a biocatalytic approach to 2-azido-2-aryl-1-ols.

An Miao M Liu Wanyi W Zhou Xiaoying X Ma Ran R Wang Huihui H Cui Baodong B Han Wenyong W Wan Nanwei N Chen Yongzheng Y

RSC advances 20190524 29

Halohydrin dehalogenases are usually recognized as strict β-position regioselective enzymes in the nucleophile-mediated ring-opening of epoxides. Here we found the HheG from <i>Ilumatobacter coccineus</i> exhibited excellent α-position regioselectivity in the azide-mediated ring-opening of styrene oxide derivatives 1a-1k, producing the corresponding 2-azido-2-aryl-1-ols 2a-2k with the yields up to 96%. ...[more]

PMID: 35516406

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Project description:Halohydrin dehalogenase HheG and its homologues are remarkable enzymes for the efficient ring opening of sterically demanding internal epoxides using a variety of nucleophiles. The enantioselectivity of the respective wild-type enzymes, however, is usually insufficient for application and frequently requires improvement by protein engineering. We herein demonstrate that the highly flexible N-terminal loop of HheG, comprising residues 39 to 47, has a tremendous impact on the activity as well as enantioselectivity of this enzyme in the ring opening of structurally diverse epoxide substrates. Thus, highly active and enantioselective HheG variants could be accessed through targeted engineering of this loop. In this regard, variant M45F displayed almost 10-fold higher specific activity than wild type in the azidolysis of cyclohexene oxide, yielding the corresponding product (1S,2S)-2-azidocyclohexan-1-ol in 96%eeP (in comparison to 49%eeP for HheG wild type). Moreover, this variant was also improved regarding activity and enantioselectivity in the ring opening of cyclohexene oxide with other nucleophiles, demonstrating even inverted enantioselectivity with cyanide and cyanate. In contrast, a complete loop deletion yielded an inactive enzyme. Concomitant computational analyses of HheG M45F in comparison to wild type enzyme revealed that mutation M45F promotes the productive binding of cyclohexene oxide and azide in the active site by establishing noncovalent C-H ··π interactions between epoxide and F45. These interactions further position one of the two carbon atoms of the epoxide ring closer to the azide, resulting in higher enantioselectivity. Additionally, stable and enantioselective cross-linked enzyme crystals of HheG M45F were successfully generated after combination with mutation D114C. Overall, our study highlights that a highly flexible loop in HheG governs the enzyme's activity and selectivity in epoxide ring opening and should thus be considered in future protein engineering campaigns of HheG.

Dataset Information

Highly α-position regioselective ring-opening of epoxides catalyzed by halohydrin dehalogenase from Ilumatobacter coccineus: a biocatalytic approach to 2-azido-2-aryl-1-ols.

Publications

Highly α-position regioselective ring-opening of epoxides catalyzed by halohydrin dehalogenase from <i>Ilumatobacter coccineus</i>: a biocatalytic approach to 2-azido-2-aryl-1-ols.

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