A family of radical halogenases for the engineering of amino-acid-based products
A family of radical halogenases for the engineering of amino-acid-based products
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DOI：
10.1038/s41589-019-0355-x
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发表时间：
2019-10-01
影响因子：
14.8
通讯作者：
Chang, Michelle C. Y.
中科院分区：
文献类型：
--
作者：
Neugebauer, Monica E.;Sumida, Kiera H.;Chang, Michelle C. Y.
合成和生物催化的结合，通过将酶的高选择性与合成化学提供的反应多样性相结合，为小分子合成提供了新的方法。虽然有机卤素因其生物活性和作为合成基础的用途而受到重视，但只有少数几种酶能够对未活化的C-sp3-H I键进行区域选择性卤化。在这种情况下，我们报道了BesD的结构表征，BesD是一种最近发现的来自Fe-II/ α -酮葡萄糖酸依赖家族的自由基卤化酶，它将游离氨基酸赖氨酸氯化。我们还鉴定和表征了产生单氯和二氯，以及溴化和叠氮化氨基酸的其他卤化酶。这个新的自由基卤素酶家族的底物选择性利用了氨基酸在代谢中的中心作用，使生物合成途径的工程能够提供各种各样的化合物类别，包括杂环、二胺、α -酮酸和肽。
The integration of synthetic and biological catalysis enables new approaches to the synthesis of small molecules by combining the high selectivity of enzymes with the reaction diversity offered by synthetic chemistry. While organohalogens are valued for their bioactivity and utility as synthetic building blocks, only a handful of enzymes that carry out the regioselective halogenation of unactivated C-sp3-H I bonds have previously been identified. In this context, we report the structural characterization of BesD, a recently discovered radical halogenase from the Fe-II/alpha-ketogluturate-dependent family that chlorinates the free amino acid lysine. We also identify and characterize additional halogenases that produce mono-and dichlorinated, as well as brominated and azidated, amino acids. The substrate selectivity of this new family of radical halogenases takes advantage of the central role of amino acids in metabolism and enables engineering of biosynthetic pathways to afford a wide variety of compound classes, including heterocycles, diamines, alpha-keto acids and peptides.