PMID- 37081856
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230422
IS  - 1867-3880 (Print)
IS  - 1867-3899 (Electronic)
IS  - 1867-3880 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Feb 8
TI  - The Discovery of Imine Reductases and their Utilisation for the Synthesis of 
      Tetrahydroisoquinolines.
PG  - e202201126
LID - 10.1002/cctc.202201126 [doi]
LID - e202201126
AB  - Imine reductases (IREDs) are NADPH-dependent enzymes with significant 
      biocatalytic potential for the synthesis of primary, secondary, and tertiary 
      chiral amines. Their applications include the reduction of cyclic imines and the 
      reductive amination of prochiral ketones. In this study, twenty-nine novel IREDs 
      were revealed through genome mining. Imine reductase activities were screened at 
      pH 7 and 9 and in presence of either NADPH or NADH; some IREDs showed good 
      activities at both pHs and were able to accept both cofactors. IREDs with Asn and 
      Glu at the key 187 residue showed preference for NADH. IREDs were also screened 
      against a series of dihydroisoquinolines to synthesise tetrahydroisoquinolines 
      (THIQs), bioactive alkaloids with a wide range of therapeutic properties. 
      Selected IREDs showed high stereoselectivity, as well high THIQ yields (>90 %) 
      when coupled to a glucose-6-phosphate dehydrogenase for NADPH cofactor recycling.
CI  - (c) 2022 The Authors. ChemCatChem published by Wiley-VCH GmbH.
FAU - Cardenas-Fernandez, Max
AU  - Cardenas-Fernandez M
AD  - Department of Biochemical Engineering University College London Gower Street, 
      Bernard Katz Building London WC1E 6BT UK.
AD  - School of Biosciences University of Kent K ent CT2 7NJ UK.
FAU - Roddan, Rebecca
AU  - Roddan R
AUID- ORCID: 0000-0002-9406-9011
AD  - Department of Chemistry University College London 20 Gordon Street London WC1H 
      0AJ UK.
FAU - Carter, Eve M
AU  - Carter EM
AD  - Department of Chemistry University College London 20 Gordon Street London WC1H 
      0AJ UK.
FAU - Hailes, Helen C
AU  - Hailes HC
AUID- ORCID: 0000-0001-5574-4742
AD  - Department of Chemistry University College London 20 Gordon Street London WC1H 
      0AJ UK.
FAU - Ward, John M
AU  - Ward JM
AUID- ORCID: 0000-0002-4415-5544
AD  - Department of Biochemical Engineering University College London Gower Street, 
      Bernard Katz Building London WC1E 6BT UK.
LA  - eng
PT  - Journal Article
DEP - 20230111
PL  - Germany
TA  - ChemCatChem
JT  - ChemCatChem
JID - 101520610
PMC - PMC10107726
OTO - NOTNLM
OT  - Imine reductases
OT  - activity screening
OT  - phylogenetic analysis
OT  - reductive amination
OT  - tetrahydroisoquinolines
COIS- None declared.
EDAT- 2023/04/21 06:41
MHDA- 2023/04/21 06:42
PMCR- 2023/04/17
CRDT- 2023/04/21 02:14
PHST- 2022/09/15 00:00 [received]
PHST- 2022/12/13 00:00 [revised]
PHST- 2023/04/21 06:42 [medline]
PHST- 2023/04/21 06:41 [pubmed]
PHST- 2023/04/21 02:14 [entrez]
PHST- 2023/04/17 00:00 [pmc-release]
AID - CCTC202201126 [pii]
AID - 10.1002/cctc.202201126 [doi]
PST - ppublish
SO  - ChemCatChem. 2023 Feb 8;15(3):e202201126. doi: 10.1002/cctc.202201126. Epub 2023 
      Jan 11.