Asymmetric Ketone Reduction by Imine Reductases

Lenz, Maike; Meisner, Jan; Quertinmont, Leann; Lutz, Stefan; Kästner, Johannes; Nestl, Bettina M.

doi:10.1002/cbic.201600647

Cited by 53 publications

(40 citation statements)

References 26 publications

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“…Moreover, NR and Zt_SDR also accept “common” ketones as substrates. This is remarkable as, to date, promiscuous reductase activity of SDRs with C=N bonds, and vice versa of IREDs with C=O bonds, has only been observed with highly reactive compounds . Along with the physiological enone reductase activity of NR, this highlights the pluripotency featured by some SDRs .…”

Section: Methodsmentioning

confidence: 89%

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Exploiting the Catalytic Diversity of Short‐Chain Dehydrogenases/Reductases: Versatile Enzymes from Plants with Extended Imine Substrate Scope

et al. 2018

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Numerous short-chain dehydrogenases/reductases (SDRs) have found biocatalytic applications in C=O and C=C (enone) reduction. For NADPH-dependent C=N reduction, imine reductases (IREDs) have primarily been investigated for extension of the substrate range. Here, we show that SDRs are also suitable for a broad range of imine reductions. The SDR noroxomaritidine reductase (NR) is involved in Amaryllidaceae alkaloid biosynthesis, serving as an enone reductase. We have characterized NR by using a set of typical imine substrates and established that the enzyme is active with all four tested imine compounds (up to 99 % conversion, up to 92 % ee). Remarkably, NR reduced two keto compounds as well, thus highlighting this enzyme family's versatility. Using NR as a template, we have identified an as yet unexplored SDR from the Amaryllidacea Zephyranthes treatiae with imine-reducing activity (≤95 % ee). Our results encourage the future characterization of SDR family members as a means of discovering new imine-reducing enzymes.

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Section: Methodsmentioning

confidence: 89%

“…Examples of enzymatic reduction promiscuity have been reported for highly reactive iminium and activated keto substrates . NR, however, displays catalytic versatility with nonactivated substrates occurring in vivo .…”

Section: Methodsmentioning

confidence: 99%

Exploiting the Catalytic Diversity of Short‐Chain Dehydrogenases/Reductases: Versatile Enzymes from Plants with Extended Imine Substrate Scope

et al. 2018

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“…The samples were extracted with methyl tert ‐butyl ether (MTBE) and derivatized with acetic anhydride. Finally, the organic phases were analyzed by gas chromatography (GC) as described previously (Figures S7 and S8 in the Supporting Information) …”

Section: Methodsmentioning

confidence: 99%

“…Finally,t he organic phases were analyzed by gas chromatography (GC) as described previously ( Figures S7 and S8 in the Supporting Information). [37]…”

Section: Biotransformation and Sample Preparation For The Gcmentioning

confidence: 99%

Switching the Cofactor Specificity of an Imine Reductase

Borlinghaus

Nestl

2017

ChemCatChem

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“…Moreover, in Catharanthus roseus a medium‐chain alcohol dehydrogenase homologue that possesses iminium‐reducing activity has been found . Conversely, Nestl and co‐workers most recently proposed a carbonyl reductase (side) activity by two IREDs exposed to a highly reactive ketone substrate …”

Section: Methodsmentioning

confidence: 99%

Extended Catalytic Scope of a Well‐Known Enzyme: Asymmetric Reduction of Iminium Substrates by Glucose Dehydrogenase

et al. 2017

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NADP(H)-dependent imine reductases (IREDs) are of interest in biocatalytic research due to their ability to generate chiral amines from imine/iminium substrates. In reaction protocols involving IREDs, glucose dehydrogenase (GDH) is generally used to regenerate the expensive cofactor NADPH by oxidation of d-glucose to gluconolactone. We have characterized different IREDs with regard to reduction of a set of bicyclic iminium compounds and have utilized H NMR and GC analyses to determine degree of substrate conversion and product enantiomeric excess (ee). All IREDs reduced the tested iminium compounds to the corresponding chiral amines. Blank experiments without IREDs also showed substrate conversion, however, thus suggesting an iminium reductase activity of GDH. This unexpected observation was confirmed by additional experiments with GDHs of different origin. The reduction of C=N bonds with good levels of conversion (>50 %) and excellent enantioselectivity (up to >99 % ee) by GDH represents a promiscuous catalytic activity of this enzyme.

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Asymmetric Ketone Reduction by Imine Reductases

Cited by 53 publications

References 26 publications

Exploiting the Catalytic Diversity of Short‐Chain Dehydrogenases/Reductases: Versatile Enzymes from Plants with Extended Imine Substrate Scope

Exploiting the Catalytic Diversity of Short‐Chain Dehydrogenases/Reductases: Versatile Enzymes from Plants with Extended Imine Substrate Scope

Switching the Cofactor Specificity of an Imine Reductase

Extended Catalytic Scope of a Well‐Known Enzyme: Asymmetric Reduction of Iminium Substrates by Glucose Dehydrogenase

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