De novo design of porphyrin-containing proteins as efficient and stereoselective catalysts

• 全文链接

从头设计含卟啉的蛋白质作为高效且立体选择性的催化剂

关键词：

来源：

Science

全文链接：

//agri.nais.net.cn/topic/downloadFile/c3dc5e74-88c3-4607-840e-9628647af2d4

来源地址：

https://www.science.org/doi/10.1126/science.adt7268

资源所属：

饲料用酶工程

类型：

学术文献

语种：

中文

原文发布日期：

2025-05-08

摘要：

De novo design of protein catalysts with high efficiency and stereoselectivity provides an attractive approach toward the design of environmentally benign catalysts. Here, we design proteins that incorporate histidine-ligated synthetic porphyrin and heme ligands. Four of 10 designed proteins catalyzed cyclopropanation with an enantiomeric ratio greater than 99:1. A second class of proteins were designed to catalyze a silicon-hydrogen insertion and were optimized by directed evolution in whole cells. The evolved proteins incorporated features unlikely to be generated by computational design alone, including a proline in an α helix. Molecular dynamics simulations showed that as the proteins evolved toward higher activity, their conformational ensembles narrowed to favor more productive conformations. Our work demonstrates that efficient de novo protein catalysts are designable and should be useful for manifold chemical processes.