Li, Wei-8, Gao, Feng-4, Kleinbeck-Riniker, Florian and Gallou, Fabrice (2026) Engineered aldehyde dehydrogenases for amide bond formation. Science, 391 (6784). pp. 1-12. ISSN 0036-8075

Abstract

Amide bond formation is widely used in pharmaceutical synthesis and typically constructed from acids using stoichiometric coupling reagents. Here, we repurposed aldehyde dehydrogenases into unprecedented oxidative amidases (OxiAms) by creating a more hydrophobic and spacious catalytic pocket for amines to capture the thioester intermediate. This biocatalyst efficiently facilitates the formation of amide bonds between diverse aldehydes and amines without the use of stoichiometric coupling reagents, providing an alternative way for amide synthesis. Remarkably, we also developed a two-step enzymatic cascade to synthesize amides from broadly available alcohols. Furthermore, this biocatalytic strategy enabled the redesign of synthetic routes for five drug molecules. Our findings highlight the potential of OxiAms in advancing the synthesis of structurally diverse drug molecules through efficient amide bond formation.

Item Type:	Article
Date Deposited:	26 Mar 2026 00:45
Last Modified:	26 Mar 2026 00:45
URI:	https://oak.novartis.com/id/eprint/58818