Enzymic Synthesis of L-Fucose and Analogs

Wong, Chi‐Huey; Alajarı́n, Ramón; Morís-Varas, Francisco; Blanco, Olga María; García‐Junceda, Eduardo

doi:10.1021/jo00127a052

Cited by 34 publications

(15 citation statements)

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“…Interestingly, this diastereofacial selectivity was the inverse of that found for the natural acceptor, l-lactaldehyde, and other non-natural aldehydes. [24][25][26] In these cases, the DHAP-FucA complex attacks the carbonyl component at the si face, although the formation of diastereoisomers (3-30 %), epimeric at the C-4 position, has been reported. [14] On the other hand, FucA was highly stereoselective towards both enantiomers of Cbz-alaninal with approximately 99 % de of the expected 4R diastereoisomer (iminocyclitols 13-15) being formed.…”

Section: Resultsmentioning

confidence: 99%

Aldol Additions of Dihydroxyacetone Phosphate to N‐Cbz‐Amino Aldehydes Catalyzed by L‐Fuculose‐1‐Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor Aldehyde

Espelt¹,

Bujons²,

Parella

et al. 2005

Chemistry A European J

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The potential of L-fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N-protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100 mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N-protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)-N-Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N-Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N-Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N-Cbz-glycinal and N-Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after C-C bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results.

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Section: Resultsmentioning

confidence: 99%

Aldol Additions of Dihydroxyacetone Phosphate to N‐Cbz‐Amino Aldehydes Catalyzed by L‐Fuculose‐1‐Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor Aldehyde

Espelt¹,

Bujons²,

Parella

et al. 2005

Chemistry A European J

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“…77 This describes the enzymatic synthesis of L-fucose (6) from dihydroxyacetone phosphate (3) (DHAP) and DL-lactaldehyde (2) catalysed by L-fuculose-1-phosphate aldolase, followed by reaction with acid phosphatase and L-fucose isomerase (Fig 9). Two methods were carried out: stepwise and sequential syntheses.…”

Section: Enzymatic Synthesis Of L-fucosementioning

confidence: 99%

L-Fucose: occurrence, physiological role, chemical, enzymatic and microbial synthesis

Vanhooren

Vandamme

1999

J. Chem. Technol. Biotechnol.

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An easy source of unusual monosaccharides such as the 6-deoxyhexose, L-fucose are certain microbial extracellular polysaccharides (EPS), best known for their thickening, gelling or emulsifying properties. L-Fucose and L-fucose containing oligosaccharides have potential application in the medical ®eld in preventing tumour cell colonisation of the lung (anticancer effect), in controlling the formation of white blood cells (anti-in¯ammatory effect), in the treatment of rheumatoid arthritis, in the synthesis of antigens for antibody production (rational immunisation) and in cosmeceuticals as skin moisturing agent. L-Fucose production via chemical synthesis is laborious and suffers from low yield, while direct extraction from brown algae is costly and subject to seasonal variations in supply volume and quality. Enzymatic synthesis is currently under investigation. Chemical or enzymatic hydrolysis of L-fucose-rich microbial EPS opens up a new route towards ef®cient L-fucose production. This review deals with the properties, occurrence, physiological roles, chemical, enzymatic and microbial production of L-fucose.

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“…To date, two methods of enzymatically producing l -fucose from l -fuculose, the ketose form of l -fucose, have been developed. Although l -fuculose is more expensive and scarce in nature than l -fucose, l -fuculose can be synthesized as an intermediate from readily available resources, such as common sugars [12–14]. One approach is based on the reverse reaction for the l -fucose metabolic pathway, in which l -fuculose can be synthesized by an aldolase-catalyzed reaction between lactaldehyde and dihydroxyacetone phosphate (DHAP), followed by acid phosphatase-catalyzed dephosphatation [12].…”

Section: Introductionmentioning

confidence: 99%

“…Although l -fuculose is more expensive and scarce in nature than l -fucose, l -fuculose can be synthesized as an intermediate from readily available resources, such as common sugars [12–14]. One approach is based on the reverse reaction for the l -fucose metabolic pathway, in which l -fuculose can be synthesized by an aldolase-catalyzed reaction between lactaldehyde and dihydroxyacetone phosphate (DHAP), followed by acid phosphatase-catalyzed dephosphatation [12]. Such an in vitro strategy can be further expanded to microbial fermentation using glucose as carbon source for l -fucose synthesis by constructing a metabolically engineered pathway.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic synthesis of l-fucose from l-fuculose using a fucose isomerase from Raoultella sp. and the biochemical and structural analyses of the enzyme

Kim

Nam

et al. 2019

Biotechnol Biofuels

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Backgroundl-Fucose is a rare sugar with potential uses in the pharmaceutical, cosmetic, and food industries. The enzymatic approach using l-fucose isomerase, which interconverts l-fucose and l-fuculose, can be an efficient way of producing l-fucose for industrial applications. Here, we performed biochemical and structural analyses of l-fucose isomerase identified from a novel species of Raoultella (RdFucI).ResultsRdFucI exhibited higher enzymatic activity for l-fuculose than for l-fucose, and the rate for the reverse reaction of converting l-fuculose to l-fucose was higher than that for the forward reaction of converting l-fucose to l-fuculose. In the equilibrium mixture, a much higher proportion of l-fucose (~ ninefold) was achieved at 30 °C and pH 7, indicating that the enzyme-catalyzed reaction favors the formation of l-fucose from l-fuculose. When biochemical analysis was conducted using l-fuculose as the substrate, the optimal conditions for RdFucI activity were determined to be 40 °C and pH 10. However, the equilibrium composition was not affected by reaction temperature in the range of 30 to 50 °C. Furthermore, RdFucI was found to be a metalloenzyme requiring Mn2+ as a cofactor. The comparative crystal structural analysis of RdFucI revealed the distinct conformation of α7–α8 loop of RdFucI. The loop is present at the entry of the substrate binding pocket and may affect the catalytic activity.ConclusionsRdFucI-catalyzed isomerization favored the reaction from l-fuculose to l-fucose. The biochemical and structural data of RdFucI will be helpful for the better understanding of the molecular mechanism of l-FucIs and the industrial production of l-fucose.

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Enzymic Synthesis of L-Fucose and Analogs

Cited by 34 publications

References 0 publications

Aldol Additions of Dihydroxyacetone Phosphate to N‐Cbz‐Amino Aldehydes Catalyzed by L‐Fuculose‐1‐Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor Aldehyde

Aldol Additions of Dihydroxyacetone Phosphate to N‐Cbz‐Amino Aldehydes Catalyzed by L‐Fuculose‐1‐Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor Aldehyde

L-Fucose: occurrence, physiological role, chemical, enzymatic and microbial synthesis

Enzymatic synthesis of l-fucose from l-fuculose using a fucose isomerase from Raoultella sp. and the biochemical and structural analyses of the enzyme

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