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Content archived on 2024-05-24

Glycosylation engineering for novel antobiotics

Objective

Medically-important polyketide antibiotics produced by streptomycetes often contain deoxysugar residues essential for their function. Altering these sugars would be a powerful route to new antibiotics. Increasing microbial resistance makes this an urgent need. This proposal is to study production of novel glycosylated polyketides, using knowledge of the biosynthetic pathways to deoxyhexoses (6-DOH). The word includes:
1) complementation of mutants in deoxysugar pathways to generate hybrid glycosylated compounds
2) Production of hybrid antibiotics by adding aglycones to cells containing gene sets specifying synthesis of a deoxysugar, together with cloned glycosyltransferases (GTases)
3) use of enzymes for synthesis of 6-DOH in production of activated substrates for Gtases
4) use of purified GTases with activated deoxysugars, for biotransformation of aglycones 5) DNA shuffling of GTases genes and selection in vivo for bioactivity.

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Topic(s)

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Funding Scheme

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
EU contribution
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Address
80,Tennis Court Road, 80
CB2 1GA CAMBRIDGE
United Kingdom

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Total cost

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Participants (6)

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