7WNW

Crystal structure of Imine Reductase Mutant(M5) from Actinoalloteichus hymeniacidonis in complex with NADPH

Summary for 7WNW

• Entry DOI: 10.2210/pdb7wnw/pdb
• Descriptor: 3-hydroxyisobutyrate dehydrogenase-like beta-hydroxyacid dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: imine reductase, nadph, ired, oxidoreductase
• Biological source: Actinoalloteichus hymeniacidonis
• Total number of polymer chains: 2
• Total formula weight: 72008.13

Authors

Zhand, J.,Chen, R.,Gao, S. (deposition date: 2022-01-19, release date: 2022-04-06, Last modification date: 2023-11-29)

Primary citation

Zhang, J.,Liao, D.,Chen, R.,Zhu, F.,Ma, Y.,Gao, L.,Qu, G.,Cui, C.,Sun, Z.,Lei, X.,Gao, S.S.
Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering.
Angew.Chem.Int.Ed.Engl., 61:e202201908-e202201908, 2022

PubMed Abstract: Although imine reductases (IREDs) are emerging as attractive reductive aminases (RedAms), their substrate scope is still narrow, and rational engineering is rare. Focusing on hydrogen bond reorganization and cavity expansion, a concise strategy combining rational cavity design, combinatorial active-site saturation test (CAST), and thermostability engineering was designed, that transformed the weakly active IR-G36 into a variant M5 with superior performance for the synthesis of (R)-3-benzylamino-1-Boc-piperidine, with a 4193-fold improvement in catalytic efficiency, a 16.2 °C improvement in T , and a significant increase in the e.e. value from 78 % (R) to >99 % (R). M5 exhibits broad substrate scope for the synthesis of diverse azacycloalkylamines, and the reaction was demonstrated on a hectogram-scale under industrially relevant conditions. Our study provides a compelling example of the preparation of versatile and efficient IREDs, with exciting opportunities in medicinal and process chemistry as well as synthetic biology.

PubMed: 35322515
DOI: 10.1002/anie.202201908

Experimental method

X-RAY DIFFRACTION (2.13 Å)