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Chemoenzymatic Synthesis of Sialic Acid Derivatives Using Immobilized N‐ Acetylneuraminate Lyase in a Continuous Flow Reactor
Author(s) -
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.
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201900146
Subject(s) - chemistry , sialic acid , flow chemistry , continuous flow , lyase , combinatorial chemistry , organic chemistry , biochemistry , catalysis , enzyme , biochemical engineering , engineering
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.