Objective
Sugar residues frequently play an important role in the structure/ function relationships of many complex bioactive molecules, and more specifically in the macrolide antibiotics. Macrolides are complex polyketides which are produced mostly by streptomycetes. Their basic structure consists of a cyclic macrolactone to which are attached one or several 6-deoxyhexoses (6-DOH). More generally, more than 80 different derivatives of 6-DOH occur in low-molecular weight natural products. As the synthetic chemistry of sugars remains highly problematic, there is an urgent requirement for new approaches opening the way to sugar replacement on lactone rings and other aglycones. Indeed, as microbial resistance to antibiotics remains an acute problem, there is a continual need for innovative products. Therefore, much is now expected from the development of novel technologies such as molecular biology and enzyme technology for the essential modification of existing biomolecules or the design of novel bioactive products. The main goal of this proposal is therefore to unite the efforts of industrial and basic research laboratories to generate a new technology giving access to modification of 6-DOH residues on macrolide antibiotics and related compounds. The proposed work will encompass: 1) elucidation of the biosynthetic pathways of several 6-deoxy-hexoses in order to be able to modify them by minimal genetic changes, 2) expression and characterization of a number of glycosyl transferases (GTs) and fine biochemical characterization of one of them (including crystallography), in order to reach a better understanding of their structure-function relationships, 3) molecular engineering of GTs by DNA shuffling as a means of changing sugar attachment on lactone rings, 4) downstream processing of enzymes involved in the biosynthesis of 6-DOH, and 5) biofermentation and purification of aglycones in order to generate substrates for analysis of GT activities.
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 genetics DNA
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
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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
93235 Romainville
France
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.