Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds

Winkler, Christoph; Tasnádi, Gábor; Clay, Dorina; Hall, Mélanie; Faber, Kurt

doi:10.1016/j.jbiotec.2012.03.023

Cited by 146 publications

(119 citation statements)

References 106 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…The proton donated by the Tyr residue is replenished by a water molecule. Finally, a reduced NAD(P)H molecule reduces the oxidized flavin cofactor [104].…”

Section: Ec 131: Ene Reductasesmentioning

confidence: 99%

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Vidal

Kelly

Mordaka

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

248

147

View full text Add to dashboard Cite

A B S T R A C T NAD(P)H-dependent oxidoreductases catalyze the reduction or oxidation of a substrate coupled to the oxidation or reduction, respectively, of a nicotinamide adenine dinucleotide cofactor NAD(P)H or NAD(P) + . NAD(P)Hdependent oxidoreductases catalyze a large variety of reactions and play a pivotal role in many central metabolic pathways. Due to the high activity, regiospecificity and stereospecificity with which they catalyze redox reactions, they have been used as key components in a wide range of applications, including substrate utilization, the synthesis of chemicals, biodegradation and detoxification. There is great interest in tailoring NAD(P)H-dependent oxidoreductases to make them more suitable for particular applications. Here, we review the main properties and classes of NAD(P)H-dependent oxidoreductases, the types of reactions they catalyze, some of the main protein engineering techniques used to modify their properties and some interesting examples of their modification and application.

show abstract

“…The proton donated by the Tyr residue is replenished by a water molecule. Finally, a reduced NAD(P)H molecule reduces the oxidized flavin cofactor [104].…”

Section: Ec 131: Ene Reductasesmentioning

confidence: 99%

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Vidal

Kelly

Mordaka

et al. 2018

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

248

147

View full text Add to dashboard Cite

show abstract

“…They are typically used as ene-reductases to catalyze the bio-reduction of alkenes to generate up to two stereogenic centers. These NAD(P)H-dependent oxidoreductases contain a non-covalently bound cofactor flavin mononucleotide (FMN) and are capable of reducing a variety of activated alkenes, including ␣,␤-unsaturated ketones, aldehydes, nitroalkenes, carboxylic acids and derivatives [9,10]. The products often serve as versatile synthons in pharmaceutical and fine chemical industries [7,11,12].…”

Section: Introductionmentioning

confidence: 99%

Two “classical” Old Yellow Enzymes from Chryseobacterium sp. CA49: Broad substrate specificity of Chr-OYE1 and limited activity of Chr-OYE2

Pei

2016

Journal of Molecular Catalysis B: Enzymatic

View full text Add to dashboard Cite

“…Podem ser encontradas isoladas (MONTI et al, 2011) ou contidas em células íntegras de micro-organismos (BRENNA et al, 2012;CARBALLEIRA et al, 2009;FABER, 2011;BOMMARIUS, 2011;WINKLER et al, 2012). Entre elas, as desidrogenases destacam-se pelo seu amplo uso em reações de biorredução de substratos pró-quirais para a produção de compostos opticamente ativos (Esquema 1) (CARBALLEIRA et al, 2009;FABER, 2011;BOMMARIUS, 2011).…”

Section: Biorredução Dos Compostos Carbonílicos αβ-Insaturados Mediaunclassified

“…Entre elas, as desidrogenases destacam-se pelo seu amplo uso em reações de biorredução de substratos pró-quirais para a produção de compostos opticamente ativos (Esquema 1) (CARBALLEIRA et al, 2009;FABER, 2011;BOMMARIUS, 2011). A álcool desidrogenase (ADH), também conhecida por carbonila redutase, tem sido comumente utilizada para a preparação de álcoois enriquecidos enantiomericamente por meio da redução de grupos carbonilas (CARBALLEIRA et al, 2009;FABER, 2011;MILAGRE et al, 2009;MONTI et al, 2011;NAKAMURA et al, 2003 Entre os diversos micro-organismos que apresentam a ene redutase e, consequentemente, a capacidade de reduzir assimetricamente a ligação dupla (MULLER; HAUER; ROSCHE, 2006;WINKLER et al, 2012), o Saccharomyces cerevisiae ocupa um lugar especial, pois historicamente, ele foi o primeiro biocatalisador adotado para sínteses assimétricas e gerou compostos quirais com alto ee (BRENNA et al, 2012;SERVI, 1990).…”

Section: Biorredução Dos Compostos Carbonílicos αβ-Insaturados Mediaunclassified

“…A taxa relativa da redução C=C versus C=O depende das enzimas e dos compostos envolvidos (KERGOMARD; RENARD;VESCHAMBRE, 1982;STUERMER et al, 2007). Por exemplo, a competitiva redução da carbonila em olefinas ativadas é menor em cetonas do que em aldeídos e a distribuição do produto está relacionada com a quantidade e velocidade relativa de redução de cada uma dessas enzimas presentes nos micro-organismos (FABER, 2011;STUERMER et al, 2007;WINKLER et al, 2012).…”

Section: Biorredução Dos Compostos Carbonílicos αβ-Insaturados Mediaunclassified

See 1 more Smart Citation

Biorredução de compostos carbonílicos alfa,beta-insaturados visando à síntese de substâncias opticamente ativas

Silva¹

View full text Add to dashboard Cite

Palavras-chave: Biorredução, compostos carbonílicos α,β-insaturados, micro-organismo, Saccharomyces cerevisiae. In recent years, the preparation of enantiomerically pure compounds has become a concern and a challenge to the industry. This fact is a consequence of the tenuous relationship between the spatial structure of substances and the different flavors, odors, pharmacokinetic and pharmacodynamic processes and toxicity that they play in the body. In this context, the asymmetric synthesis of α-alkyl substituted optically active carbonyl compounds has received great attention because they are important building blocks in the synthesis of chiral drugs and natural products. Thus, this study aimed to develop methodologies that allow the preparation of this enantiomerically pure compounds by controlling the formation of stereogenic centers using biocatalysis. To this end, various activated olefins substituted with electron withdrawing groups (carbonyl) were synthesized using two procedures, aldol condensation and esterification reactions. These α,β-unsaturated carbonyl compounds were obtained in good yields (48-94%) and subjected to the biocatalytic reduction mediated by whole cells of microorganisms. Initially, we used the olefin (E)-3-methyl-4-phenyl-3-buten-2-one (51a) as a model substrate for the optimization of the experimental conditions and determine wich one provide the product with better conversion and enantiomeric purity. In these tests, we evaluated various reaction parameters such as the composition of the reaction medium (aqueous, biphasic and buffer), the presence of additives (glucose and phase transfer catalyst), different microorganisms and adsorbing effect of using Amberlite XAD-7. Thus, the biorreduction in aqueous medium, without additives, mediated by LSC-II yeast and with the application of Amberlite XAD-7 was the reaction condition that presented the best enantiomeric excess (81%) and was selected for a methodological study that evaluated the steric and electronic effects of the substituents. It was observed that the substituent in the β-position of the aryl group, the size increase of the α-substituent and the presence of an ester group had an important role in the stereoselectivity of the reaction. Finally, application of the methodology on muguesia enantioselective synthesis, a floral fragrance, was evaluated. The results obtained showed the high potential of the methodology in chemoselective bioreduction of α,β-unsaturated carbonyl compounds and preparation of optically active substances.

show abstract

Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds

Cited by 146 publications

References 106 publications

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Review of NAD(P)H-dependent oxidoreductases: Properties, engineering and application

Two “classical” Old Yellow Enzymes from Chryseobacterium sp. CA49: Broad substrate specificity of Chr-OYE1 and limited activity of Chr-OYE2

Biorredução de compostos carbonílicos alfa,beta-insaturados visando à síntese de substâncias opticamente ativas

Contact Info

Product

Resources

About