But the status quo methods to make them from carboxylic acids tend to rely on wasteful coupling reagents. So researchers, especially those in pharma, are interested in finding new, more-efficient strategies<\/a>.<\/p>\n Now Lei and his team at Peking University, partnering with scientists from Novartis, have engineered a well-known enzyme<\/a> to form this well-known molecular linkage from aldehydes instead of acids (Science 2025, DOI:10.1126\/science.adw3365).<\/p>\n Donald Hilvert<\/a> of the Swiss Federal Institute of Technology (ETH), Zurich, who was not involved in the work, calls it \u201can exemplary demonstration of how enzyme scaffolds can be repurposed for new chemistry.\u201d<\/p>\n The authors\u2019 approach is deceptively simple: take an aldehyde dehydrogenase enzyme, which naturally converts aldehydes to acids, and get it to react with an amine instead of water. But actually making that happen was no small feat, Lei says.<\/p>\n It took a deep understanding of the biocatalytic mechanism, three rounds of engineering, and more than 10 crystal structures of the binding pocket, Lei says, but eventually they succeeded in creating an amine-selective enzyme.<\/p>\n Lei and his team designed their new \u201coxidative aminases\u201d to work on a wide variety of pharma-relevant aldehydes and amines, including aromatic amines. The researchers also showed that they could use the enzymes in a cascade reaction with an alcohol dehydrogenase to make amides from alcohols in a single operation.<\/p>\n Finally, the researchers demonstrated how their enzymatic strategy could shave steps and cost from the synthesis of two US Food and Drug Administration\u2013approved pharmaceuticals: vadadustat, used for treating anemia associated with kidney disease, and Novartis\u2019s precision cancer drug imatinib<\/a>. The new route to imatinib uses a \u201cdirt cheap\u201d dialdehyde starting material and \u201cyou don\u2019t waste any single atom,\u201d which reduces purification-related costs, Lei says.<\/p>\n Overall, Hilvert says, the paper is \u201ca very clever, elegant showcase of how structural insights and enzyme engineering can drive innovation.\u201d Having a new addition to the toolkit of ways to make amides is a welcome development, and the researchers were clearly thinking about how to make their method appealing to pharma companies, he adds.<\/p>\n
![\"Brianna](\"https:\/\/www.newsbeep.com\/il\/wp-content\/uploads\/2025\/10\/2025-bri.jpg\")
<\/a><\/p>\n