Glycosylation of Model and ‘Lower’ Organisms - The Sugar Code - page 142

Figure 8.2 The glycosylation potential of yeast.
(a) Yeast species add more mannose residues
to their N -glycans than is the case in other
species, but some yeasts also transfer galac-

tose to their N -glycans. (b) The tendency to
have mannose-rich glycans in yeast is also seen
with their O -glycans. (c) The glycolipids of yeast
also tend to be simple.

the key mannosyltransferases required for outer chain formation in yeast, have
been targeted in order to reduce N - glycan size. Further efforts to ' humanise ' yeast,
in order that their glycosylation is closer to that of our own and so facilitate the
use of recombinant proteins as therapeutic agents, have included introducing a
number of genes required for complex N - glycan modifi cations; this has been
accomplished in Pichia pastoris [4]. One company, GlycoFi (now a subsidiary of
Merck), has been 'built' on this technology. The large size of naturally occurring
yeast N -glycans is not the only problem; they are also antigenic, which is of distinct
disadvantage when one wishes to produce a recombinant protein for pharmaceuti-
cal use. Furthermore, some yeast N -glycans carry not just poly- - mannose; the

fi ssion yeast Schizosaccharomyces pombe produces N - glycans modifi ed with galac-
tose residues, which can be pyruvate-substituted (see Figure 8.2), whereas
the pathogenic yeast Candida albicans has peripheral

α

β - linked mannose on its

N - glycans [3] .
A further complication when considering yeast glycosylation is that their
O -glycans, unlike those of mammals, tend to contain, dependent on the species,