Engineered aldehyde dehydrogenases for amide bond formation

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. Our findings…

• NN
  National Natural Science Foundation of China

  Awards: 92253305, 22193073, 22337002, 22322701, 22193073, 22337002, and 92253305
• BN
  Beijing National Laboratory for Molecular Sciences

  Award: BNLMS-CXX-202106