7XR5

Crystal structure of imine reductase with NAPDH from Streptomyces albidoflavus

Summary for 7XR5

• Entry DOI: 10.2210/pdb7xr5/pdb
• Descriptor: 6-phosphogluconate dehydrogenase NAD-binding, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57-nonadecaoxanonapentacontane-1,59-diol, ... (4 entities in total)
• Functional Keywords: streptomyces albidoflavus, nadp, r-imine reductase, oxidoreductase
• Biological source: Streptomyces albidoflavus
• Total number of polymer chains: 4
• Total formula weight: 134485.92

Authors

Zhang, J.,Chen, R.C.,Gao, S.S. (deposition date: 2022-05-09, release date: 2022-10-19, Last modification date: 2024-05-01)

Primary citation

Zhang, J.,Li, X.,Chen, R.,Tan, X.,Liu, X.,Ma, Y.,Zhu, F.,An, C.,Wei, G.,Yao, Y.,Yang, L.,Zhang, P.,Wu, Q.,Sun, Z.,Wang, B.G.,Gao, S.S.,Cui, C.
Actinomycetes-derived imine reductases with a preference towards bulky amine substrates.
Commun Chem, 5:123-123, 2022

PubMed Abstract: Since imine reductases (IREDs) were reported to catalyze the reductive amination reactions, they became particularly attractive for producing chiral amines. Though diverse ketones and aldehydes have been proved to be excellent substrates of IREDs, bulky amines have been rarely transformed. Here we report the usage of an Increasing-Molecule-Volume-Screening to identify a group of IREDs (IR-G02, 21, and 35) competent for accepting bulky amine substrates. IR-G02 shows an excellent substrate scope, which is applied to synthesize over 135 amine molecules as well as a range of APIs' substructures. The crystal structure of IR-G02 reveals the determinants for altering the substrate preference. Finally, we demonstrate a gram-scale synthesis of an analogue of the API sensipar via a kinetic resolution approach, which displays ee >99%, total turnover numbers of up to 2087, and space time yield up to 18.10 g L d.

PubMed: 36697820
DOI: 10.1038/s42004-022-00743-y

Experimental method

X-RAY DIFFRACTION (1.58 Å)