Efficient and Stereoselective Enzymatic Synthesis of Multisubstituted α,β-Diamino Acid

• 全文链接

多取代 α,β-二氨基酸的高效立体选择性酶促合成

关键词：

来源：

ACS Catalysis

全文链接：

//agri.nais.net.cn/topic/downloadFile/6fbd37db-bc2c-4575-89e1-ee277343c6d0

来源地址：

https://pubs.acs.org/accacs/article/doi/10.1021/acscatal.6c03940/5356875/Efficient-and-Stereoselective-Enzymatic-Synthesis

资源所属：

饲料用酶工程

类型：

学术文献

语种：

英语

原文发布日期：

2026-08-28

摘要：

α,β-Diamino acids are privileged motifs present in numerous bioactive natural products and synthetic molecules, yet their asymmetric synthesis remains challenging and limited in scope. Herein, we repurpose l-threonine aldolases to catalyze a stereoselective intermolecular Mannich-type reaction, enabling the direct and scalable synthesis of densely functionalized α,β-diamino acids. By exploiting enzyme sequence diversity, we accessed more than 50 derivatives from simple precursors with high efficiency (up to 97% yield) and selectivity (up to >99% d.r. and >99% e.r.). The reaction achieves total turnover numbers of up to 18,000 and titers reaching 77.4 g L–1, representing the highest reported productivity for this class of biocatalytic transformation and meeting key benchmarks for industrial application. Mechanistic investigations suggest that the deprotonation of glycine contributes to the rate-determining step of the highly efficient catalytic cycle. Selected derivatives were shown to effectively suppress osteoclastogenesis, identifying a chemotype with potential for osteoporosis intervention.