Chemoenzymatic synthesis of sialic acid derivatives using immobilized N-acetylneuraminate lyase in a continuous flow reactor

Victor R.L.J. Bloemendal, Sam J. Moons, Jurriaan J.A. Heming, Mohamed Chayoua, Olaf Niesink, Jan C.M. van Hest, Thomas J. Boltje, Floris P.J.T. Rutjes (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The synthesis of N-acetylneuraminic acid (Neu5Ac) derivatives is drawing more and more attention in glycobiology research because of the important role of sialic acids in e. g. cancer, bacterial, and healthy cells. Chemical preparation of these carbohydrates typically relies on multistep synthetic procedures leading to low overall yields. Herein we report a continuous flow process involving N-acetylneuraminate lyase (NAL) immobilized on Immobead 150P (Immobead-NAL) to prepare Neu5Ac derivatives. Batch experiments with Immobead-NAL showed equal activity as the native enzyme. Moreover, by using a fivefold excess of either N-acetyl-D-mannosamine (ManNAc) or pyruvate the conversion and isolated yield of Neu5Ac were significantly improved. To further increase the efficiency of the process, a flow setup was designed providing a chemoenzymatic entry into a series of N-functionalized Neu5Ac derivatives in conversions of 48–82%, and showing excellent stability over 1 week of continuous use. (Figure presented.).

LanguageEnglish
Pages2443-2447
JournalAdvanced Synthesis and Catalysis
Volume361
Issue number11
Early online date4 Apr 2019
DOIs
StatePublished - 8 May 2019

Fingerprint

N-acetylneuraminate lyase
N-Acetylneuraminic Acid
Derivatives
Acids
Sialic Acids
Carbohydrates
Pyruvic Acid
Enzymes
Cells
Experiments

Keywords

  • enzyme immobilization
  • flow chemistry
  • N-acetylneuraminate lyase
  • N-acetylneuraminic acid

Cite this

Bloemendal, Victor R.L.J. ; Moons, Sam J. ; Heming, Jurriaan J.A. ; Chayoua, Mohamed ; Niesink, Olaf ; van Hest, Jan C.M. ; Boltje, Thomas J. ; Rutjes, Floris P.J.T./ Chemoenzymatic synthesis of sialic acid derivatives using immobilized N-acetylneuraminate lyase in a continuous flow reactor. In: Advanced Synthesis and Catalysis. 2019 ; Vol. 361, No. 11. pp. 2443-2447
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abstract = "The synthesis of N-acetylneuraminic acid (Neu5Ac) derivatives is drawing more and more attention in glycobiology research because of the important role of sialic acids in e. g. cancer, bacterial, and healthy cells. Chemical preparation of these carbohydrates typically relies on multistep synthetic procedures leading to low overall yields. Herein we report a continuous flow process involving N-acetylneuraminate lyase (NAL) immobilized on Immobead 150P (Immobead-NAL) to prepare Neu5Ac derivatives. Batch experiments with Immobead-NAL showed equal activity as the native enzyme. Moreover, by using a fivefold excess of either N-acetyl-D-mannosamine (ManNAc) or pyruvate the conversion and isolated yield of Neu5Ac were significantly improved. To further increase the efficiency of the process, a flow setup was designed providing a chemoenzymatic entry into a series of N-functionalized Neu5Ac derivatives in conversions of 48–82{\%}, and showing excellent stability over 1 week of continuous use. (Figure presented.).",
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Chemoenzymatic synthesis of sialic acid derivatives using immobilized N-acetylneuraminate lyase in a continuous flow reactor. / Bloemendal, Victor R.L.J.; Moons, Sam J.; Heming, Jurriaan J.A.; Chayoua, Mohamed; Niesink, Olaf; van Hest, Jan C.M.; Boltje, Thomas J.; Rutjes, Floris P.J.T. (Corresponding author).

In: Advanced Synthesis and Catalysis, Vol. 361, No. 11, 08.05.2019, p. 2443-2447.

Research output: Contribution to journalArticleAcademicpeer-review

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