Deoxyribose 5-phosphate aldolase as a catalyst in asymmetric aldol condensation

Chen, Lih-Ren; Dumas, David P.; Wong, Chi Huey

doi:10.1021/ja00028a050

Cited by 115 publications

(80 citation statements)

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“…Although considerable progress based on non-biological methods has been made, these methods generally require low temperature and organic solvent to achieve high asymmetric induction. However, enzyme-catalyzed aldol condensations can occur at neutral pH and room temperature and display the great potential in the coming future [3]. The class I aldolase, 2-deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4), reversibly catalyzes the aldol reaction of acetaldehyde with D-glyceraldehyde-3-phosphate to form 2-deoxyribose-5-phosphate via a Schiff base intermediate between the active-site lysine and acetaldehyde [4,5].…”

Section: Introductionmentioning

confidence: 99%

The Fed-Batch Production of a Thermophilic 2-Deoxyribose-5-Phosphate Aldolase (DERA) in Escherichia coli by Exponential Feeding Strategy Control

Pei

Wang

Qiu

et al. 2010

Appl Biochem Biotechnol

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2-Deoxyribose-5-phosphate aldolase (DERA) catalyzes a sequential aldol reaction useful in synthetic chemistry. In this work, the effect of a feeding strategy on the production of a thermophilic DERA was investigated in fed-batch cultures of recombinant Escherichia coli BL21 (pET303-DERA008). The predetermined specific growth rate (micro(set)) was evaluated at 0.20, 0.15, and 0.10 h(-1), respectively. The DERA concentration and volumetric productivity were associated with micro(set). The cells synthesized the enzyme most efficiently at micro(set) = 0.15 h(-1). The maximum enzyme concentration (5.12 g/L) and total volumetric productivity (0.256 g L(-1) h(-1)) obtained were over 10 and five times higher than that from traditional batch cultures. Furthermore, the acetate concentration remained at a relatively low level, less than 0.4 g/L, under this condition which would not inhibit cell growth and target protein expression. Thus, a specific growth rate control strategy has been successfully applied to induce fed-batch cultures for the maximal production of the thermophilic 2-deoxyribose-5-phosphate aldolase.

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Section: Introductionmentioning

confidence: 99%

The Fed-Batch Production of a Thermophilic 2-Deoxyribose-5-Phosphate Aldolase (DERA) in Escherichia coli by Exponential Feeding Strategy Control

Pei

Wang

Qiu

et al. 2010

Appl Biochem Biotechnol

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“…Scheme 1. The key enzymatic aldol condensation of 7 and acetaldehyde yields 8, which is subsequently converted to 1; we have selectively 13 C-labelled the positions marked with an asterisk (*); other positions that may be isotopically substituted are marked with°or with ∆ and ᭞ have become popular and powerful tools [8] in organic synthesis, an enzymatic aldol condensation process was exploited to construct the furanose ring from 7 and acetaldehyde. For this reaction, only the DHAP needs to be prepared in labelled form as acetaldehyde is commercially available in three differently labelled forms.…”

Section: Introductionmentioning

confidence: 99%

Chemo-Enzymatic Synthesis of Thymidine13C-Labelled in the 2′-Deoxyribose Moiety

Ouwerkerk¹,

Boom²,

Lugtenburg³

et al. 2000

Eur. J. Org. Chem.

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A synthesis of [3′,4′‐13C2]thymidine (1) is described in which [13C2]acetic acid (2) is converted into the nucleoside in twelve steps with 9% overall yield. D‐2‐Deoxyribose‐5‐phosphate aldolase (DERA, EC 4.1.2.4) and triosephosphate isomerase (TPI, EC 5.3.1.1) are used for the stereocontrolled formation of D‐[3,4‐13C2]‐2‐deoxyribose‐5‐phosphate (8) from [2,3‐13C2]dihydroxyacetone monophosphate (DHAP, 7) and acetaldehyde in 80% yield. The route permits the introduction of isotopically enriched carbon atoms at any position or combination of positions in the furanose ring and the product can be coupled with any of the four naturally occurring base moieties.

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“…[6,21,23] Although fluoroacetone has been shown to be a competent nucleophilic substrate for deoxyribose-5-phosphate aldolase (DERA), carboncarbon bond formation does not occur from the fluorine-bearing carbon, and thus a new fluorine-bearing stereocentre is not formed. [25] However, despite some reports to the contrary, [20,24] fluoropyruvate has been shown to be a viable substrate for several Class I lysine-dependent pyruvate aldolases (Table 1). In such reactions, there are four possible stereoisomeric products, and the stereocontrol exerted by the aldolase in each case is indicated in Table 1.…”

Section: Fluoropyruvate As a Nucleophile In Aldolase-catalysed Reactionsmentioning

confidence: 99%

Aldolase-catalysed stereoselective synthesis of fluorinated small molecules

Windle

Berry

Nelson

2017

Current Opinion in Chemical Biology

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The introduction of fluorine has been widely exploited to tune the biological functions of small molecules. Indeed, around 20% of leading drugs contain at least one fluorine atom. Yet, despite profound effects of fluorination on conformation, there is only a limited toolkit of reactions that enable stereoselective synthesis of fluorinated compounds. Aldolases are useful catalysts for the stereoselective synthesis of bioactive small molecules; however, despite fluoropyruvate being a viable nucleophile for some aldolases, the potential of aldolases to control the formation of fluorine-bearing stereocentres has largely been untapped. Very recently, it has been shown that aldolase-catalysed stereoselective carboncarbon bond formation with fluoropyruvate as nucleophile enable the synthesis of many -fluoro -hydroxy carboxyl derivatives. Furthermore, an understanding of the structural basis for the stereocontrol observed in these reactions is beginning to emerge.Here, we review the application of aldolase catalysis in the stereocontrolled synthesis of chiral fluorinated small molecules, and highlight likely areas for future developments.

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Deoxyribose 5-phosphate aldolase as a catalyst in asymmetric aldol condensation

Cited by 115 publications

References 0 publications

The Fed-Batch Production of a Thermophilic 2-Deoxyribose-5-Phosphate Aldolase (DERA) in Escherichia coli by Exponential Feeding Strategy Control

The Fed-Batch Production of a Thermophilic 2-Deoxyribose-5-Phosphate Aldolase (DERA) in Escherichia coli by Exponential Feeding Strategy Control

Chemo-Enzymatic Synthesis of Thymidine13C-Labelled in the 2′-Deoxyribose Moiety

Aldolase-catalysed stereoselective synthesis of fluorinated small molecules

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