工程化醛脱氢酶实现酰胺键合成

Lei Gao1,2†, Xiang Qiu1†, Jun Yang1,3†, Kangdelong Hu1†, Peilin Li1, Wei Li4, Feng Gao4, Fabrice Gallou5, Florian Kleinbeck5, Xiaoguang Lei1,3* Amide bond formation is widely used in pharmaceutical synthesis, typically involving stoichiometric coupling reagents to activate carboxylic acid substrates for a condensation reaction. As an alternative approach, we repurposed aldehyde dehydrogenases into oxidative amidases 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. We also developed a two-step enzymatic cascade to synthesize amides from broadly available aliphatic alcohols. This biocatalytic strategy enabled the redesign of synthetic routes for five drug molecules. …