Substrate range of acetohydroxy acid synthase I from <i>Escherichia coli</i> in the stereoselective synthesis of α‐hydroxy ketones

Engel, Stanislav; Vyazmensky, Maria; Berkovich, Dvora; Barak, Ze’ev; Chipman, David M.

doi:10.1002/bit.20275

Cited by 33 publications

(13 citation statements)

References 21 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[14] Our investigation into the substrate range of YerE revealed that this protein catalyzed the formation of (S)-acetolactate as well as (R)-PAC (Scheme 2). [15] Furthermore, ortho-substituted benzaldehydes, which are poor substrates for EcAHAS I and ZmPDC catalysts, [16,17] were efficiently converted into their corresponding (R)-2-hydroxyketones, such as 1 a (1-(2-chlorophenyl)-1-hydroxypropan-2-one) and 2 a (1-hydroxy-1-(4hydroxyphenyl)-propan-2-one), in high enantiomeric excess (Table 1). YerE also catalyzed a carboligation reaction to afford (S)-acetoin, using pyruvate and acetaldehyde as substrates.…”

mentioning

confidence: 99%

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

et al. 2010

View full text Add to dashboard Cite

Thiamine diphosphate (ThDP)-dependent enzymes are wellestablished catalysts in the field of asymmetric synthesis. [1] One of the model reactions catalyzed by these enzymes is the asymmetric CÀC bond-formation reaction between two aldehyde substrates that leads to the formation of 2-hydroxyketones in high enantioselectivities. [2] Exchange of one of the aldehyde substrates in this reaction for a ketone [3] would offer the opportunity for the catalytic asymmetric formation of chiral tertiary alcohols, which are important structural units in natural products and bioactive agents. [4,5] During the last decade, different organocatalysts have been developed for the asymmetric aldehyde-ketone cross-coupling reaction, [6] and intramolecular variants of this reaction have been reported in the literature. [7,8] Most recently, Enders and Henseler described the direct intermolecular cross-coupling between aldehydes and trifluoromethyl ketones using a bicyclic triazolium salt as the catalyst. [9] The asymmetric intermolecular non-enzymatic coupling reaction with ketone acceptors should be more difficult, owing to the lower electrophilicity of the ketone carbonyl group, and the increased steric hindrance compared with aldehyde substrates, and has not yet been reported in the literature. Herein, we present an asymmetric intermolecular aldehyde-ketone carboligation reaction using a ThDP-dependent enzyme as the catalyst (Scheme 1).Branched-chain sugars are important bioactive carbohydrates and are widely represented in nature. Using feeding experiments, it can be shown that the two-carbon branch of several of these sugar derivatives is derived from pyruvate. In 1972, Grisebach and Schmid postulated the participation of ThDP in this carboligation reaction. [10] In the biosynthetic pathway of yersiniose A, a two-carbon branched-chain 3,6di(deoxy)hexose that is found in the O-antigen of Yersinia pseudotuberculosis O:VI, the ThDP-dependent flavoenzyme YerE catalyzes the decarboxylation of pyruvate and the transfer of the activated acetaldehyde onto the carbonyl function of CDP-3,6-di(deoxy)-4-keto-d-glucose (CDP = cytidine-5'-diphosphate). [11,12] The enzymatic activity of YerE was confirmed by incubation of the protein with the enzymatically prepared physiological substrate (starting from CDP-d-glucose). The isolated product CDP-4-aceto-3,6dideoxygalactose was confirmed by NMR spectroscopy.To analyze the substrate range of the enzyme, we amplified the gene yerE from the chromosomal DNA of Y. pseudotuberculosis O:VI using a polymerase chain reaction. The gene was cloned into the pQE-60 expression vector and the recombinant protein was produced in Escherichia coli BL21(DE3) cells. The overexpressed C-terminal His-tagged YerE protein was purified to homogeneity by affinity chromatography using an Ni-NTA purification system (see the Supporting Information).The amino acid sequence of YerE is similar to that of the large subunit of E. coli acetohydroxyacid synthases (EcAHAS) (31 % identity). AHAS successfully catalyzed the ThDP-dependent ...

show abstract

mentioning

confidence: 99%

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

et al. 2010

View full text Add to dashboard Cite

show abstract

“…3. Among the three isoenzymes (I, II, III) in Escherichia coli, AHAS I appears to be the most effective in the chiral synthesis of PAC [9].…”

Section: Acetohydroxy Acid Synthase (Ahas)mentioning

confidence: 97%

“…AHAS I has the ability to accept a wide variety of substituted benzaldehydes [9]. Ortho-substituted aromatic aldehydes are poorer substrates for the formation of a-hydroxy ketones than their meta-and para-substituted isomers.…”

Section: Acetohydroxy Acid Synthase (Ahas)mentioning

confidence: 99%

Thiamine Pyrophosphate Dependent Enzyme Catalyzed Reactions: Stereoselective C–C Bond Formations in Water

Demir¹,

Ayhan

Sopacı

2007

CLEAN Soil Air Water

View full text Add to dashboard Cite

Enzymes are biodegradable and renewable resources that utilize water as the reaction solvent. Reactions catalyzed by enzymes are among the most effective, selective, and , green' processes available today. The advantages of using biocatalysts include their high degree of regio-and stereo-specificity, versatility, and high reaction rates under mild reaction conditions. Enzyme catalyzed enantioselective C -C bond formation reactions are rather important aspects of synthetic organic chemistry. Thiamine pyrophosphate (TPP) dependent enzymes, especially, have an important role in the stereoselective formation of C -C bonds. This review covers the recent advances in enzyme catalyzed asymmetric C -C bond formation using the most pronounced thiamine pyrophosphate dependent enzymes: acetohydroxyacid synthase, benzaldehyde lyase, benzoylformate decarboxylase, pyruvate decarboxylase, and phenylpyruvate decarboxylase. These enzymes are all capable of acyloin-type condensation reactions in water under mild conditions, in turn leading to chiral a-hydroxy ketones, which are versatile building blocks for the pharmaceutical and chemical industries. IntroductionThe , green chemistry' concept as proposed by P. T. Anastas in 1991 includes the design, development, and application of chemical processes and products in such a way as to avoid substances that are hazardous to human health and the environment [1]. The biocatalytic reactions that employ either enzymes or whole cells are well suited for green chemistry because mild reaction conditions are applied in these reactions by lowering the energy requirements; fewer by-products are formed as they are highly chemo-, regio-, and stereoselective, and multi-step chemical syntheses can be achieved within just a few steps via biocatalysis [1].Optically active a-oxyfunctionalized compounds, in particular, carboxylic acids, aldehydes, and ketones are indispensable building blocks for asymmetric synthesis due to their versatile functional groups, which can be easily transformed to other functionalities, e. g., diols, halo or amino derivatives, and epoxides [2].Of these a-oxyfunctionalized compounds, a-hydroxy ketones (acyloins) are especially important, see Fig. 1. The classical methodology for the synthesis of these compounds involves acyloin and benzoin condensation. The former includes C -C bond formation under reductive conditions while the latter involves C -C bond breaking,

show abstract

“…not sensitive to the feedback inhibition of the product R-PAC, and has a broad spectrum of substrates. 14,15 But this protein has its own shortcomings. Research has shown that the natural abundance of AHAS is low and its stability is poor.…”

Section: -17mentioning

confidence: 99%

An improved enzymatic method for the preparation of (R)-phenylacetyl carbinol

Liu

Xian

2017

RSC Adv.

View full text Add to dashboard Cite

(R)-Phenylacetyl carbinol (R-PAC) is one of the key chiral a-hydroxyketones utilized as a synthon in the synthesis of a number of pharmaceuticals having a-and b-adrenergic properties. An improved procedure for the preparation of the compound using the glutathione S-transferase-tag fused catalytic subunit of Escherichia coli acetohydroxyacid synthase I as a catalyst was established in this study. The results showed that under the optimized conditions the target molecule was able to be obtained with an isolated yield of 80.6% and an ee value of higher than 98%. This method could not only ease the preparation of R-PAC, but promote the synthetic applications of E. coli AHAS I as well.

show abstract

Substrate range of acetohydroxy acid synthase I from Escherichia coli in the stereoselective synthesis of α‐hydroxy ketones

Cited by 33 publications

References 21 publications

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

Enantioselective Intermolecular Aldehyde–Ketone Cross‐Coupling through an Enzymatic Carboligation Reaction

Thiamine Pyrophosphate Dependent Enzyme Catalyzed Reactions: Stereoselective C–C Bond Formations in Water

An improved enzymatic method for the preparation of (R)-phenylacetyl carbinol

Contact Info

Product

Resources

About