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首页> 外文期刊>Journal of Chemical Technology & Biotechnology >A concise synthesis of single-enantiomer ss-lactams and ss-amino acids using Rhodococcus globerulus
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A concise synthesis of single-enantiomer ss-lactams and ss-amino acids using Rhodococcus globerulus

机译：使用球形红球菌的简明合成单一对映体β-内酰胺和β-氨基酸

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BACKGROUND: Pharmaceutical companies continue to evaluate ss-amino acids and ss-lactams in a range of drug candidates. The development of a highly efficient and selective bioresolution of cyclic ss-lactam substrates could yield enantiopure lactams and ss-amino acids with medicinal potential. The aim of this work was to discover and develop a biocatalyst capable of selectively hydrolysing ss-lactam substrates. RESULTS: Screening of our in-house culture collection led to the discovery of a microorganism, Rhodococcus globerulus (NCIMB 41042) with P-lactamase activity. Whole-cell bioresolutions of the ss-lactams 1-4 were successfully carried out and in all cases enantiomeric excesses of the residual lactam and amino acid product were found to be greater than 98%. For one example, the bioresolution was optimised to operate at 60 g L-1 substrate concentration with a 20% wt/wt cell paste loading. CONCLUSIONS: A microorganism, Rhodococcus globerulus (NCIMB 41042), capable of selectively hydrolysing a range of cyclic ss-lactams, has been discovered. A scalable whole-cell bioresolution process has been developed, leading to the synthesis of multigram quantities of enantiomerically pure ss-lactams and ss-amino acids. (c) 2007 Society of Chemical Industry.
机译：背景：制药公司继续在一系列候选药物中评估SS-氨基酸和SS-内酰胺。环状ss-内酰胺底物的高效和选择性生物拆分的发展可能产生对映体纯的内酰胺和具有药用潜力的ss-氨基酸。这项工作的目的是发现和开发一种能够选择性水解ss-内酰胺底物的生物催化剂。结果：我们内部培养物收集的筛选导致发现了一种具有P-内酰胺酶活性的微生物，球形红球菌（NCIMB 41042）。 ss-内酰胺1-4的全细胞生物拆分已成功进行，在所有情况下，残留内酰胺和氨基酸产物的对映体过量均大于98％。举一个例子，生物分辨率被优化为在60 g L-1底物浓度下以20％wt / wt的细胞糊负载量运行。结论：已发现一种能够选择性水解一系列环状β-内酰胺的微生物，球形红球菌（NCIMB 41042）。已经开发了可扩展的全细胞生物分解方法，导致合成了几克数量的对映体纯的ss-内酰胺和ss-氨基酸。 （c）2007年化学工业协会。

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