Objective
Deoxy and amino sugars are often constituents of secondary metabolites of clinical importance such as polyketide and glycopeptide antibiotics.
The emergence of antibiotic resistance has created an urgent need for novel antibiotics active against resistant bacterial strains. Altering the composition of sugar appendages in glycoconjugates holds promise for creating new products with novel biological activities. Significant progress has been made via genetic and biochemical methods to develop effective glycosylation strategies in vivo, however yields are generally low, product analysis is difficult and the production of new glycosylated antimicrobial agents in vivo is limited by inhibition of cell growth or death.
The in vitro glycosylation using isolated glycosyltransferases could be a promising solution to overcome this hurdle.
The aims of this research project are:
(i) identification and characterization of the N-acetylglucosamine deacetylase involved in the biosynthesis of the glycopeptide antibiotic teicop lanin;
(ii) cloning and characterisation of the mannosyltransferase involved in the biosynthesis of teicoplanin;
(iii) determination of the order of glycosylation events leading to the maturation of teicoplanin;
(iv) in vitro synthesis of novel vancomycin/ teicoplanin glycopeptides.
The enzymes will be obtained by PCR amplification of genes from the Actinoplanes teichomyceticus teicoplanin producer strain and following expression of cloned genes in E. coli.
Upon purification the enzymes will be used in vitro assays to study their activity towards their natural and non-natural substrates and to generate novel glycopeptides.
The purified enzymes will also be subjected to protein-protein interaction studies and crystallisation in order to understand the structural biology of these systems.
This work will provide valuable information about the final steps of teicoplanin biosynthesis and pave the way to the in vitro generation of novel glycosylated antibiotics.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance antibiotic resistance
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
CAMBRIDGE
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.