Serine hydroxymethyl transferase from Streptococcus thermophilus and L-threonine aldolase from Escherichia coli as stereocomplementary biocatalysts for the synthesis of β-hydroxy-α,ω-diamino acid derivatives
Serine hydroxymethyl transferase from Streptococcus thermophilus and L-threonine aldolase from Escherichia coli as stereocomplementary biocatalysts for the synthesis of β-hydroxy-α,ω-diamino acid derivatives
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DOI：
10.1002/chem.200800031
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Clapes, Pere
中科院分区：
文献类型：
--
作者：
Gutierrez, Mariana L.;Garrabou, Xavier;Clapes, Pere
以嗜热链球菌丝氨酸羟甲基转移酶和L苏氨酸缩醛酶为立体互补催化剂，研究了甘氨酸与N-氨基醛和苯氧基乙醛的羟醛加成反应。这两种苏氨酸缩醛酶都是低专一性的L-别苏氨酸缩醛酶，通过调节反应温度、甘氨酸浓度和反应介质等反应参数，可以得到转化率为34-60%的L-红血球非对映异构体，而长链转移酶得到的L-苏氨酸非对映体的转化率为30：70-16：84，转化率为40-68%。SHMT是所描述的最具立体选择性的L-苏氨酸缩醛酶之一。这是由于其活性与温度的依赖关系：在4℃时，SHMT具有很高的合成活性，而对L-苏氨酸的逆转醛活性可以忽略不计。因此，动力学的L-赤潮异构体在很大程度上受到了人们的青睐，反应几乎是不可逆转的，具有高度的立体选择性，进而产生了很好的转化率。制备的N-CBZ-γ-氨基-β-羟基-α-氨基酸衍生物与氢氧化钾(1M)反应，可自发生成2-恶唑烷酮的β-羟基和γ-氨基的衍生物。该反应可能有助于对产物进行进一步的化学操作。
A novel serine hdroxymethyl transferase from Streptococcus thermophilus (SHMT) and a L-threonine aldolase from Escherichia coli (LTA) were used as stereocomplementary biocatalysts for the aldol addition of glycine to N-Cbz amino aldehydes and benzyloxyacetaldehyde (Cbz = benzyloxycarbonyl). both threonine aldolases were classified as low-specific L-allo-threonine aldolases, and by manipulating reaction parameters, such as temperature, glycine concentration, and reaction media, SHMT yielded exclusively L-erythro diastereomers in 34-60% conversion, whereas LTA gave L-threo diastereomers in 30:70 to 16:84 diastereomeric ratios and with 40-68% conversion to product. SHMT is among the most stereoselective L-threonine aldolases described. This is due, among other things, to its activity-temperature dependence: at 4 degrees C SHMT has high synthetic activity but negligible retroaldol activity on L-threonine. Thus, the kinetic L-erythro isomer was largely favored and the reactions were virtually irreversible, highly stereoselective, and in turn, gave excellent conversion. It was also found that treatment of the prepared N-Cbz-gamma-amino-beta-hydroxy-alpha-amino acid derivatives with potassium hydroxide (1 M) resulted in the spontaneous formation of 2-oxazolidinone derivatives of the beta-hydroxyl and gamma-amino groups in quantitative yield. This reaction might be useful for further chemical manipulations of the products.