Page 385 - Cascade_Biocatalysis_Integrating_Stereoselective_and_Environmentally_Friendly_Reactions

361

17
Enzymatic Generation of Sialoconjugate Diversity

Wolf-Dieter Fessner, Ning He, Dong Yi, Peter Unruh, and Marion Knorst

17.1
Introduction

Sialic acids are a family of acidic nine-carbon sugars that represent one of the most
important constituents of cell-surface glycoconjugates in biological systems [1, 2].
These compounds occur naturally as the most abundant outermost carbohydrates
on vertebrate cells as constituents of glycoproteins, gangliosides, and related
glycoconjugate structures, where they are generally α-ketosidically bound, either
α(2,3)- or α(2,6)-linked to hexoses or α(2,8)-linked to other sialic acids (Figure 17.1)
[2]. The predominant member of the sialic acid family is 5-acetamido-d-glycero-d-
galacto-2-nonulosonic acid (N-acetylneuraminic acid (Neu5Ac), 1; Scheme 17.1).
Owing to their exposed position and anionic charge, sialic acids are ideally suited to
participate in carbohydrate–protein interactions that mediate cellular recognition
phenomena, and recent advances in glycobiology have revealed the significant role
of complex sialylated oligosaccharide structures as key elements in fertilization,
embryogenesis, cancer metastasis, blood coagulation, inflammation, and bacterial
or viral infection [3].
In microorganisms, sialic acids are found in a few taxonomically scattered bacte-
rial and fungal species, which establish either symbiotic or parasitic relationships
with animal hosts [4, 5]. While a few of these microorganisms can synthesize sialic
acids de novo, others use host sialic acids for the sialylation of their own cell-surface
molecules [6]. The presence of mammalian-type sialic acid conjugates decorating
the microbial cell surface is considered to be a virulence factor because it correlates
with the fact that most of these mucosal microorganisms are pathogenic (such as
Neisseria meningitidis, N. gonorrhoeae, Hemophilus influenzae,or Campylobacter jejuni
species). Apparently, sialylation is used as a molecular mimicry strategy by imitating
the sialylated glycosylation pattern of their hosts, thereby allowing these bacterial
intruders to evade the host’s innate immune response [7]. Deaminated structures
such as 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (KDN; 3) or 2-keto-3-deoxy-
d-manno-octonic acid (KDO) also occur frequently as components of various animal
glycoproteins and glycosphingolipids [8] or of the lipooligosaccharide portion of
the outer membrane of various gram-negative bacteria, respectively [9].

Cascade Biocatalysis: Integrating Stereoselective and Environmentally Friendly Reactions, First Edition.
Edited by Sergio Riva and Wolf-Dieter Fessner.
c 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.