Modular multi-enzyme cascades enable green and sustainable synthesis of non-canonical amino acids from glycerol

• 全文链接

模块化多酶级联实现由甘油绿色可持续合成非经典氨基酸

关键词：

来源：

Nature Communications

全文链接：

//agri.nais.net.cn/topic/downloadFile/7e341337-ae08-4e22-b9f5-260492afe23d

来源地址：

//agri.nais.net.cn/topic/downloadFile/7e341337-ae08-4e22-b9f5-260492afe23d

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：

2025-08-29

摘要：

Non-canonical amino acids (ncAAs) bearing diverse functional groups hold transformative potential in drug discovery, protein engineering, and biomaterial science. However, their industrial-scale production remains constrained by the inefficiency, high cost, and environmental burden of conventional chemical and enzymatic methods. Here, we present a modular multi-enzyme cascade platform that leverages glycerol—an abundant and sustainable byproduct of biodiesel production—as a low-cost substrate for ncAAs synthesis. Directed evolution of O-phospho-l-serine sulfhydrylase (OPSS) enhances the catalytic efficiency of C–N bond formation by 5.6-fold, enabling the efficient synthesis of triazole-functionalized ncAAs. By integrating a plug-and-play enzymatic strategy, our system enables gram- to decagram-scale production of 22 ncAAs with C–S, C–Se, and C–N side chains and can be readily scaled up to a 2 liter reaction system. Notably, water is the sole byproduct, and all products exhibit an atomic economy of >75%, highlighting the environmental compatibility of this platform. This work establishes a green, cost-effective, and industrially viable approach to expanding amino acid diversity, providing a versatile toolkit for applications in pharmaceuticals, synthetic biology, and next-generation biomaterials.