Catalytic Scope of the Thiamine‐Dependent Multifunctional Enzyme Cyclohexane‐1,2‐dione Hydrolase

Loschonsky, Sabrina; Waltzer, Simon; Fraas, Sonja; Wacker, Thomas; Andrade, Susana L. A.; Kroneck, Peter M. H.; Müller, Michael

doi:10.1002/cbic.201300673

Cited by 13 publications

(16 citation statements)

References 18 publications

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“…Two notable donor substrates accepted by the double variant are methyl pyruvate and butane‐2,3‐dione. This reactivity is similar to that of the enzymes from acetoin metabolism …”

Section: Introductionsupporting

confidence: 64%

“…This reactivity is similar to that of the enzymesf rom acetoin metabolism. [11,12] Despite its fundamental biocatalytic and biosynthetic significance, YpYerE has not been structurally characterizeda so fy et, although numerousa ttempts to obtain crystalsh ave been made. Withint his paper,w ep resent our efforts to gain deeper insight into the catalysis of ketone-accepting, ThDP-dependent enzymes by identifying an enzyme homologoust oYpYerE, PpYerE from Pseudomonas protegens,f or which we werea ble to obtain crystalss uitablef or X-ray structure elucidation;t his enzyme shows homology to YpYerE in terms of the associated biosynthetic gene clustera nd the reactions catalyzed.…”

Section: Introductionmentioning

confidence: 99%

“…11 and products 12-15 of PpYerE-catalyzed transformations. Conditions: ketone 8-11 (20 mm), pyruvate (6,50mm), PpYerE (1 mg mL À1 ), KP i buffer( 50 mm,p H8.0, containing3mm MgCl 2 , 0.5 mm ThDP), 20 %D MSO [only added for assaysw ith b-tetralone (10)and 1-phenoxypropan-2-one (11)],total volume 1.5 mL;[a] cyclohexane-1,2-dione (9,100 mm), pyruvate(6,20mm).…”

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confidence: 99%

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Structural and Mutagenesis Studies of the Thiamine‐Dependent, Ketone‐Accepting YerE from Pseudomonas protegens

et al. 2018

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A wide range of thiamine diphosphate (ThDP)-dependent enzymes catalyze the benzoin-type carboligation of pyruvate with aldehydes. A few ThDP-dependent enzymes, such as YerE from Yersinia pseudotuberculosis (YpYerE), are known to accept ketones as acceptor substrates. Catalysis by YpYerE gives access to chiral tertiary alcohols, a group of products difficult to obtain in an enantioenriched form by other means. Hence, knowledge of the three-dimensional structure of the enzyme is crucial to identify structure-activity relationships. However, YpYerE has yet to be crystallized, despite several attempts. Herein, we show that a homologue of YpYerE, namely, PpYerE from Pseudomonas protegens (59 % amino acid identity), displays similar catalytic activity: benzaldehyde and its derivatives as well as ketones are converted into chiral 2-hydroxy ketones by using pyruvate as a donor. To enable comparison of aldehyde- and ketone-accepting enzymes and to guide site-directed mutagenesis studies, PpYerE was crystallized and its structure was determined to a resolution of 1.55 Å.

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“…Two notable donor substrates accepted by the double variant are methyl pyruvate and butane‐2,3‐dione. This reactivity is similar to that of the enzymes from acetoin metabolism …”

Section: Introductionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

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Structural and Mutagenesis Studies of the Thiamine‐Dependent, Ketone‐Accepting YerE from Pseudomonas protegens

et al. 2018

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“…Other than for the already discussed synthesis of acetoin, the nonphysiological carboligation activity of this enzyme has also recently been exploited to produce ( R )‐PAC through the condensation of pyruvate and benzaldehyde. CDH accepts a broad range of variously monosubstituted benzaldehydes (Table , Columns 3 and 4) and sterically hindered aromatic aldehydes [Table , values (a)] as substrates, giving the corresponding ( R )‐PAC analogues with elevated ee values (92–99 %) …”

Section: Aliphatic‐aromatic and Aromatic‐aliphatic Cross‐benzoin Tmentioning

confidence: 99%

“… Conditions (a) reactions catalyzed by CDH with pyruvate (2.5 equiv.) as donor Conditions (b) reactions catalyzed by Ao:DCPIP OR with methylacetoin ( 23 , 1.5 equiv.) as donor …”

Section: Aliphatic‐aromatic and Aromatic‐aliphatic Cross‐benzoin Tmentioning

confidence: 99%

Thiamine‐Diphosphate‐Dependent Enzymes as Catalytic Tools for the Asymmetric Benzoin‐Type Reaction

2016

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Benzoin-type reactions allow the generation of α- hydroxy ketones through the (formal) carboligation of two alde- hyde reactants. The synthetic relevance of the products and the wide distribution of the α-hydroxy ketone functionality in bioactive natural compounds have provided the motivation for intensive research efforts directed towards the development of ever more efficient and selective catalysts for reactions of this class. As in many other areas of study, the solution developed in nature – that is, the utilization of thiamine-diphosphate-dependent (ThDP-dependent) enzymes – also in this case allows levels of chemo- and stereoselectivity currently unattainable by biomimetic organocatalysts to be achieved. Here we present an overview of the structural diversity of the α-hydroxy ketone motif achievable through ThDP-dependent enzyme catalysis. Details relating to structure–activity relationships and to ra- tional mutagenesis approaches for improving the catalytic per- formances of wild-type enzymes are also illustrated

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(S)‐Selectivity in Phenylacetyl Carbinol Synthesis Using the Wild‐Type Enzyme Acetoin:Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis

et al. 2016

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Thiamine diphosphate (ThDP)-dependent enzymes are well known biocatalysts for the asymmetric synthesis of α-hydroxy ketones with preferential (R)selectivity. Pharmaceutically relevant phenylacetyl carbinol (PAC) is prepared with absolute (S)-configuration only in few occasions using enzyme variants suitably designed through rational site-directed mutagenesis approaches. Herein, we describe the synthesis of (S)-phenylacetyl carbinol products with extended reaction scope employing the readily available wild-type ThDP-dependent enzyme acetoin:dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR) from Bacillus licheniformis. On a semipreparative scale, cross-benzoin-like condensations of methylacetoin (donor) and differently substituted benzaldehydes proceed with almost complete chemoselectivity yielding the target (S)-1-hydroxy-1phenylpropan-2-one derivatives with high conversion efficiencies (up to 95%) and good enantioselectivities (up to 99%).Ao:DCPIP OR accepts hydroxy-and nitro-benzaldehydes and also sterically demanding substrates such as 1naphthaldehyde and 4-(tert-butyl)benzaldehyde, which are typically poor acceptors in enzymatic transformations. The explorative synthesis of (S)-phenylpropionyl carbinol mediated by Ao:DCPIP OR via carboligation of benzaldehyde with 3,4-hexanedione is also reported.

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Catalytic Scope of the Thiamine‐Dependent Multifunctional Enzyme Cyclohexane‐1,2‐dione Hydrolase

Cited by 13 publications

References 18 publications

Structural and Mutagenesis Studies of the Thiamine‐Dependent, Ketone‐Accepting YerE from Pseudomonas protegens

Structural and Mutagenesis Studies of the Thiamine‐Dependent, Ketone‐Accepting YerE from Pseudomonas protegens

Thiamine‐Diphosphate‐Dependent Enzymes as Catalytic Tools for the Asymmetric Benzoin‐Type Reaction

(S)‐Selectivity in Phenylacetyl Carbinol Synthesis Using the Wild‐Type Enzyme Acetoin:Dichlorophenolindophenol Oxidoreductase from Bacillus licheniformis

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