9VW7

NAD(P)-dependent oxidoreductase from Kutzneria albida

Summary for 9VW7

• Entry DOI: 10.2210/pdb9vw7/pdb
• Descriptor: Dehydrogenase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SULFATE ION, ... (6 entities in total)
• Functional Keywords: imine reductase, oxidoreductase
• Biological source: Kutzneria albida DSM 43870
• Total number of polymer chains: 2
• Total formula weight: 65559.94

Authors

Huang, L.,Fu, H.G.,Yao, Z.C. (deposition date: 2025-07-16, release date: 2025-07-30, Last modification date: 2025-11-19)

Primary citation

Yao, Z.,Meng, R.,Zhou, Z.,Yu, L.,Wu, Z.,Tang, L.,Qiao, T.,Li, K.,Huang, L.,Song, D.,Fu, H.
Engineering an Imine Reductase for Enantioselective Synthesis of Atropisomeric Amides.
J.Am.Chem.Soc., 147:40616-40625, 2025

PubMed Abstract: Atropisomeric amides possess unique axial chirality arising from the rotation-restricted C-C bond and find broad application in bioactive molecules and asymmetric catalysis. However, catalytic asymmetric methods for their synthesis remain underdeveloped, with no biocatalytic approaches reported. Herein, we report the first efficient biocatalytic strategy for the atroposelective synthesis of atropisomeric amides via dynamic kinetic resolution using engineered imine reductases (IREDs). Structure-guided engineering of an IRED from provided a quadruple mutant (IRED-68-M4) capable of catalyzing the stereoconvergent synthesis of diverse napthamides and benzamides in high yields and excellent enantioselectivities (up to 98% yield, >99:1 er). Gram-scale synthesis of an axially chiral napthamide was also demonstrated. Moreover, protein X-ray crystallography and molecular modeling studies revealed the structural basis of the enhanced catalytic performance of the IRED-68-M4 variant.

PubMed: 41140043
DOI: 10.1021/jacs.5c12724

Experimental method

X-RAY DIFFRACTION (2.499 Å)