Engineered N-acetylhexosamine-active enzymes in glycoscience

0476425 - MBÚ 2018 RIV NL eng J - Journal Article
Slámová, Kristýna - Bojarová, Pavla
Engineered N-acetylhexosamine-active enzymes in glycoscience.
Biochimica et Biophysica Acta-General Subjects. Roč. 1861, č. 8 (2017), s. 2070-2087. ISSN 0304-4165. E-ISSN 1872-8006
R&D Projects: GA ČR GP13-06818P; GA MŠMT(CZ) LD15085
Institutional support: RVO:61388971
Keywords : beta-N-acetylhexosaminidase * Chitinase * Glycosynthase
OECD category: Biochemistry and molecular biology
Impact factor: 3.679, year: 2017

Background: In recent years, enzymes modifying N-acetylhexosamine substrates have emerged in numerous theoretical studies as well as practical applications from biology, biomedicine, and biotechnology. Advanced enzyme engineering techniques converted them into potent synthetic instruments affording a variety of valuable glycosides.
Scope of review: This review presents the diversity of engineered enzymes active with N-acetylhexosamine carbohydrates: from popular glycoside hydrolases and glycosyltransferases to less known oxidases, epimerases, kinases, sulfotransferases, and acetylases. Though hydrolases in natura, engineered chitinases, beta-N-acetylhex-osaminidases, and endo-beta-N-acetylglucosaminidases were successfully employed in the synthesis of defined natural and derivatized chitooligomers and in the remodeling of N-glycosylation patterns of therapeutic antibodies. The genes of various N-acetylhexosaminyltransferases were cloned into metabolically engineered microorganisms for producing human milk oligosaccharides, Lewis X structures, and human-like glycoproteins. Moreover, mutant N-acetylhexosamine-active glycosyltransferases were applied, e.g., in the construction of glycomimetics and complex glycostructures, industrial production of low-lactose milk, and metabolic labeling of glycans. In the synthesis of biotechnologically important compounds, several innovative glycoengineered systems are presented for an efficient bioproduction of G1cNAc, UDP-G1cNAc, N-acetylneuraminic acid, and of defined glycosaminoglycans.
Major conclusions: The above examples demonstrate that engineering of N-acetylhexosamine-active enzymes was able to solve complex issues such as synthesis of tailored human-like glycoproteins or industrial-scale production of desired oligosaccharides. Due to the specific catalytic mechanism, mutagenesis of these catalysts was often realized through rational solutions.

Permanent Link: http://hdl.handle.net/11104/0277981