Stereoselective synthesis of bulky 1,2-diols with alcohol dehydrogenases
Stereoselective synthesis of bulky 1,2-diols with alcohol dehydrogenases
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DOI：
10.1039/c2cy20120h
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发表时间：
2012-01-01
影响因子：
5
通讯作者：
Rother, Doerte
中科院分区：
文献类型：
--
作者：
Kulig, Justyna;Simon, Robert C.;Rother, Doerte
虽然实现乙醇脱氢酶（ADH）的生物转化是普遍的，但催化空间要求高的底物，特别是2-羟基酮的还原和氧化的酶仍然很少见。为了填补这一空白，研究了八种ADH减少大体积2-羟基酮的潜力。这些酶都表现出良好的活性沿着，具有良好的对映体选择性（ee > 99%）和非对映体选择性（de > 99%）。由于它们在底物偏好和立体选择性方面的差异，现在可以通过生物转化获得广泛的非对映体纯的1，2-二醇。使用来自Ralstonia sp.（Cupriavidus sp.）（RADH），其显示出宽的底物范围，特别是对于空间要求高的化合物。芳脂族2-羟基酮，如（R）-2-羟基-1-苯基丙-1-酮（（R）-2-HPP），比脂族或芳族醛（例如，G.苯甲醛）。此外，（R）-以及（S）-2-羟基酮以高非对映选择性（de > 99%）转化。RADH是一种在大肠杆菌中过表达的全细胞生物催化剂。大肠杆菌，纯化，并彻底表征其催化性能。
Although biotransformations implementing alcohol dehydrogenases (ADHs) are widespread, enzymes which catalyse the reduction and oxidation of sterically demanding substrates, especially 2-hydroxy ketones, are still rare. To fill this gap eight ADHs were investigated concerning their potential to reduce bulky 2-hydroxy ketones. All of these enzymes showed good activities along with excellent enantio( ee > 99%) and diastereoselectivities (de > 99%). Due to their differences in substrate preferences and stereoselectivity a broad range of diastereomerically pure 1,2-diols is now accessible via biotransformation. Best results were obtained using the alcohol dehydrogenase from Ralstonia sp. (Cupriavidus sp.) (RADH), which showed a broad substrate range, especially for sterically demanding compounds. Araliphatic 2-hydroxy ketones, like (R)-2-hydroxy-1-phenylpropan-1-one ((R)-2-HPP), were reduced much faster than aliphatic or aromatic aldehydes (e. g. benzaldehyde) under the applied conditions. Additionally (R)-as well as (S)-2-hydroxy ketones were converted with high diastereoselectivities (de > 99%). RADH, which was up to now only studied as a whole cell biocatalyst overexpressed in E. coli, was purified and thoroughly characterised concerning its catalytic properties.