LYNGBYA-KENYA

Cyp-450 biosynthesis of Lyngbya majuscula natural products

Coordinatore	UNIVERSITY OF NEWCASTLE UPON TYNE    more  Organization address address: Kensington Terrace 6 city: NEWCASTLE UPON TYNE postcode: NE1 7RU contact info Titolo: Ms. Nome: Nicola Cognome: Dolman Email: send email Telefono: +44 191 222 8984 Fax: +44 191 222 5920
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	209˙033 €
EC contributo	209˙033 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-IIF
Funding Scheme	MC-IIF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-04-26   -   2014-04-25

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY OF NEWCASTLE UPON TYNE  Organization address address: Kensington Terrace 6 city: NEWCASTLE UPON TYNE postcode: NE1 7RU contact info Titolo: Ms. Nome: Nicola Cognome: Dolman Email: send email Telefono: +44 191 222 8984 Fax: +44 191 222 5920	UK (NEWCASTLE UPON TYNE)	coordinator	209˙033.40

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 Obiettivo del progetto (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.'

Introduzione (Teaser)

A species of tropical marine cyanobacteria, Lyngbya majuscula, is the source of nearly 300 natural products. Some of them may help in the treatment of cancer, diabetes, HIV and Alzheimer's disease.