Crossing the Border: From Keto- to Imine Reduction in Short-Chain Dehydrogenases/Reductases.
asymmetric reduction
biocatalysis
enzyme
mutagenesis
rational design
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
14 09 2020
14 09 2020
Historique:
received:
16
04
2020
pubmed:
22
4
2020
medline:
8
7
2021
entrez:
22
4
2020
Statut:
ppublish
Résumé
The family of NAD(P)H-dependent short-chain dehydrogenases/reductases (SDRs) comprises numerous biocatalysts capable of C=O or C=C reduction. The highly homologous noroxomaritidine reductase (NR) from Narcissus sp. aff. pseudonarcissus and Zt_SDR from Zephyranthes treatiae, however, are SDRs with an extended imine substrate scope. Comparison with a similar SDR from Asparagus officinalis (Ao_SDR) exhibiting keto-reducing activity, yet negligible imine-reducing capability, and mining the Short-Chain Dehydrogenase/Reductase Engineering Database indicated that NR and Zt_SDR possess a unique active-site composition among SDRs. Adapting the active site of Ao_SDR accordingly improved its imine-reducing capability. By applying the same strategy, an unrelated SDR from Methylobacterium sp. 77 (M77_SDR) with distinct keto-reducing activity was engineered into a promiscuous enzyme with imine-reducing activity, thereby confirming that the ability to reduce imines can be rationally introduced into members of the "classical" SDR enzyme family. Thus, members of the SDR family could be a promising starting point for protein approaches to generate new imine-reducing enzymes.
Identifiants
pubmed: 32315494
doi: 10.1002/cbic.202000233
pmc: PMC7540013
doi:
Substances chimiques
Imines
0
Ketones
0
Short Chain Dehydrogenase-Reductases
EC 1.1.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2615-2619Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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