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References 389

enormous structural variety of natural sialoconjugates and of designed analogs for
advanced investigations into their biological profiles.
Particularly, the development of promiscuous bacterial CSS and SiaT enzymes
of the Leloir pathway is instrumental for the development of simplified, cascade-
type synthetic procedures. Structure-guided protein engineering – by using site-
directed mutagenesis based on structural modeling of substrate binding, analysis
of the natural genetic diversity, and substrate specificity studies using novel high-
throughput assay technologies – is a rapid and highly useful strategy for the in
vitro generation of improved biocatalysts for synthetic applications. The exemplary
applications listed above illustrate that the construction of new oligosaccharides
is feasible even with substrate analogs that are structurally very distant from the
natural functions of these enzymes, which facilitates rapid access to biologically
important sialylated oligosaccharide structures of high structural variability and of
amazing complexity.

Acknowledgments

This work was supported by the DAAD through a PhD scholarship for D.Y. by
the Deutsche Forschungsgemeinschaft (Grant SFB 380-B25), and by the ESF via
COST action CM0701.

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