1 research outputs found
Leloir Glycosyltransferases as Biocatalysts for Chemical Production
Glycosylation
is a chemical transformation that is centrally important
in all glycoscience and related technologies. Catalysts offering good
control over reactivity and selectivity in synthetic glycosylations
are much sought. The enzymes responsible for glycosylations in natural
biosynthesis are sugar-nucleotide-dependent (Leloir) glycosyltransferases.
Discovery-oriented synthesis and pilot batch production of oligosaccharides
and glycosylated natural products have previously relied on Leloir
glycosyltransferases. However, despite their perceived synthetic utility,
Leloir glycosyltransferases are yet to see widespread application
in industrial biocatalysis. Here we show progress and limitations
in the development of Leloir glycosyltransferases into robust biocatalytic
systems for use in glycosylations for chemical production. Obtaining
highly active and stable (whole-cell) catalysts that can promote the
desired glycosylation(s) coupled to an in situ sugar nucleotide supply
remains a difficult problem. Optimizing glycosyltransferase cascade
reactions for high process efficiency is another. Glycosylations of
some natural products (e.g., flavonoids, terpenoids) involve acceptor
substrate solubility as a special challenge for biocatalytic process
design. Strategies to overcome these problems are illustrated from
examples of integrated biocatalytic process development with this
class of enzymes