Chiral β-hydroxy α-amino acid structural motifs are interesting and common synthons present in multiple APIs and drug candidates. To access these chiral building blocks either multistep chemical syntheses are required or the application of threonine aldolases, which catalyze aldol reactions between an aldehyde and glycine. Bioinformatics tools have been utilized to identify the gene encoding threonine aldolase from Vanrija humicola and subsequent preparation of its recombinant version from E. coli fermentation. We planned to implement this enzyme as a key step to access the synthesis of our target API. Beyond this specific application, the aldolase was purified, characterized and the substrate scope of this enzyme further investigated. A number of enzymatic reactions were scaled-up and the products recovered to assess the diastereoselectivity and scalability of this asymmetric synthetic approach towards β-hydroxy α-amino acid chiral building blocks.

中文翻译：

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苏氨酸醛缩酶的鉴定及其在合成有价值的α-氨基，β-羟基结构单元中的应用。

手性β-羟基α-氨基酸的结构基序是有趣的，并且常见的合成子存在于多种API和候选药物中。为了获得这些手性结构单元，需要多步化学合成或使用苏氨酸醛缩酶，其催化醛和甘氨酸之间的醛缩反应。已经利用生物信息学工具鉴定了来自Vanrija humicola的编码苏氨酸醛缩酶的基因，并随后从大肠杆菌发酵中制备了其重组形式。我们计划将这种酶实施为访问目标API合成的关键步骤。除此特定应用外，还对醛缩酶进行了纯化，表征并进一步研究了该酶的底物范围。