Objective
The filamentous marine cyanobacterium, Lyngbya majuscula (order Oscillatoriales) is a prolific source of modular natural products, some of which have shown promise for the treatment of cancer, diabetes, HIV and Alzheimers disease. However, the failure to grow its axenic cultures (because of the lack of the nifH gene) suggests that obtaining the natural products from the cyanobacterium in sustainable yields is enigmatic. My investigations into the Kenyan L. majuscula molecular diversity established it to be encapsulated by a sheath of brightly coloured epibiotic bacteria (EB) species, representative of a group of phyla that are an especially important source of novel natural products in drug discovery. Consistent with the paucity of natural product genes (a mere 3%) observed in the L. majuscula 3L draft genome sequence, there are serious concerns on whether the nearly 300 compounds isolated pan-tropically from L. majuscula originate from the cyanobacterium or EB cohabiting with it or both. This study therefore aims to investigate the heterologous cytochrome P450 (cyp450) mediated biosynthesis of L. majuscula natural products from EB cohabiting with it. The Kenyan L. majuscula is the source of the modular homodolastatin 16 (HMDS 16) and antanapeptin A (ANTAP A). Specifically, EB will be screened for polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) megasynthase gene clusters targeting HMDS 16 and ANTAP A. Gene clusters encoding for HMDS 16, ANTAP A and cyp450 flanking the clusters will be amplified from cDNA using specific primers for the gene models. PCR amplification products will be cloned and resulting plasmids transformed into a Saccharomyces cerevisiae shuttle vector for co-expression with cyp450. Methanolic extracts of the recombinant cultures will be analysed for modular natural products and the results compared with those of EB in direct culture and of L. majuscula. Structural elucidation of natural products will utilise LC/MS/NMR spectrometry.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences biological sciences genetics genomes
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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)
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.
FP7-PEOPLE-2011-IIF
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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
NE1 7RU Newcastle Upon Tyne
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.