A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation

Nett, Nathalie; Duewel, Sabine; Schmermund, Luca; Benary, Gerrit E.; Ranaghan, Kara E.; Mulholland, Adrian J.; Opperman, Diederik J.; Hoebenreich, Sabrina

doi:10.1016/j.mcat.2021.111404

“…The demonstrated continuous Hyd1 stability over time (Supporting Information, Figure S12) is an important performance benchmark for potential commercial applications, particularly in flow [37] . Furthermore, this application is likely to extend to Ts OYE variants, which have demonstrated broad substrate acceptance, are robust in harsh conditions, and can switch enantioselectivity [38] …”

Section: Methodsmentioning

confidence: 99%

“…Zuschriften cation is likely to extend to TsOYE variants, which have demonstrated broad substrate acceptance, are robust in harsh conditions, and can switch enantioselectivity. [38] We extended this system to two commercially available ene-reductases, ENE-103 and ENE-107 (Johnson Matthey), which are typically sold as a kit with GDH and formate dehydrogenase for NAD(P)H recycling. The alkene reductions demonstrated were dimethyl itaconate (3) reduction to dimethyl (R)-methyl succinate (4) by ENE-103 and 4-phenyl-3-buten-2-one (5) reduction to 4-phenyl-2-butanone (6) by ENE-107 (Table 2), using the same protocols established for TsOYE.…”

Section: Angewandte Chemiementioning

confidence: 99%

E. coli Nickel‐Iron Hydrogenase 1 Catalyses Non‐native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme Ene‐reductases**

Srinivasan

¹

,

Cleary

²

,

Ramírez

³

et al. 2021

Angewandte Chemie

0

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A new activity for the [NiFe] uptake hydrogenase 1 of Escherichia coli (Hyd1) is presented. Direct reduction of biological flavin cofactors FMN and FAD is achieved using H 2 as a simple, completely atom-economical reductant. The robust nature of Hyd1 is exploited for flavin reduction across a broad range of temperatures (25-70 8C) and extended reaction times. The utility of this system as a simple, easy to implement FMNH 2 or FADH 2 regenerating system is then demonstrated by supplying reduced flavin to Old Yellow Enzyme "enereductases" to support asymmetric alkene reductions with up to 100 % conversion. Hyd1 turnover frequencies up to 20.4 min À1 and total turnover numbers up to 20 200 were recorded during flavin recycling. Scheme 1. Oxidized (left) and reduced (right) FMN or FAD cofactors.

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“…Ene-reductases (EREDs) from the old yellow enzyme (OYE) family are flavin-dependent enzymes that catalyze the chemo-and stereo-selective asymmetric reduction of electronically activated carbon-carbon double bonds [25,27,[60][61][62], as depicted in Scheme 8. Several examples can be found in literature illustrating the use of whole cells-catalyzed cascades coupling BVMO and ERED activities.…”

Section: Multi-step Reactions Including Ered/bvmo Activity Catalyzed ...mentioning

confidence: 99%

“…Ene-reductases (EREDs) from the old yellow enzyme (OYE) family are flavin-dependent enzymes that catalyze the chemo-and stereo-selective asymmetric reduction of electronically activated carbon-carbon double bonds [25,27,[60][61][62], as depicted in Scheme 8.…”

Section: Multi-step Reactions Including Ered/bvmo Activity Catalyzed ...mentioning

confidence: 99%

Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases

Gonzalo

¹

,

Alcántara

²

2021

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Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the recent advances for overcoming the drawbacks of using BVMOs in these techniques.

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“…Communications cation is likely to extend to TsOYE variants, which have demonstrated broad substrate acceptance, are robust in harsh conditions, and can switch enantioselectivity. [38] We extended this system to two commercially available ene-reductases, ENE-103 and ENE-107 (Johnson Matthey), which are typically sold as a kit with GDH and formate dehydrogenase for NAD(P)H recycling. The alkene reductions demonstrated were dimethyl itaconate (3) reduction to dimethyl (R)-methyl succinate (4) by ENE-103 and 4-phenyl-3-buten-2-one (5) reduction to 4-phenyl-2-butanone (6) by ENE-107 (Table 2), using the same protocols established for TsOYE.…”

Section: Angewandte Chemiementioning

confidence: 99%

E. coli Nickel‐Iron Hydrogenase 1 Catalyses Non‐native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme Ene‐reductases**

Srinivasan

¹

,

Cleary

²

,

Ramírez

³

et al. 2021

View full text Add to dashboard Cite

A new activity for the [NiFe] uptake hydrogenase 1 of Escherichia coli (Hyd1) is presented. Direct reduction of biological flavin cofactors FMN and FAD is achieved using H 2 as a simple, completely atom-economical reductant. The robust nature of Hyd1 is exploited for flavin reduction across a broad range of temperatures (25-70 8C) and extended reaction times. The utility of this system as a simple, easy to implement FMNH 2 or FADH 2 regenerating system is then demonstrated by supplying reduced flavin to Old Yellow Enzyme "enereductases" to support asymmetric alkene reductions with up to 100 % conversion. Hyd1 turnover frequencies up to 20.4 min À1 and total turnover numbers up to 20 200 were recorded during flavin recycling. Scheme 1. Oxidized (left) and reduced (right) FMN or FAD cofactors.

show abstract

A robust and stereocomplementary panel of ene-reductase variants for gram-scale asymmetric hydrogenation

Cited by 19 publications

References 52 publications

E. coli Nickel‐Iron Hydrogenase 1 Catalyses Non‐native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme Ene‐reductases**

E. coli Nickel‐Iron Hydrogenase 1 Catalyses Non‐native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme Ene‐reductases**

Multienzymatic Processes Involving Baeyer–Villiger Monooxygenases

E. coli Nickel‐Iron Hydrogenase 1 Catalyses Non‐native Reduction of Flavins: Demonstration for Alkene Hydrogenation by Old Yellow Enzyme Ene‐reductases**

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