HAHN_PFL_TETRONATES

Identification of a general biosynthetic pathway of 3-acyltetronates and further investigation of the biosynthetic pathway of the ionophoric polyethers tetronasin and tetronomycin

Coordinatore	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE    more  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Edna Cognome: Murphy Email: send email Telefono: +44 1223 333543 Fax: 1223766002
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	171˙300 €
EC contributo	171˙300 €
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-IEF-2008
Funding Scheme	MC-IEF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-08-01   -   2011-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Edna Cognome: Murphy Email: send email Telefono: +44 1223 333543 Fax: 1223766002	UK (CAMBRIDGE)	coordinator	171˙300.62

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'A main aim of the research project is the elucidation of a general biosynthetic pathway of 3-acyltetronates. For this purpose, enzymes, which were identified in the gene clusters of the phosphatase inhibitor RK-682 and the quasi-enantiomeric ionophoric polyethers tetronasin and tetronomycin to be potentially responsible for tetronate formation will be heterologously expressed in E.coli. The purified enzymes will be applied for the development of in vitro assays with synthetically prepared surrogates. Besides the identification of a distinct biosynthetic pathway of 3-acyltetronates, the use of structurally diverse synthetic precursors will allow to draw conclusions about the substrate specifity of these enzymes. After expression of further enzymes from the tetronasin and the tetronomycin gene cluster, these enzymes will also be incubated with suggestive synthetic precursor analogues. Understanding the mechanism of 3-acyltetronate formation in RK-682 and the ionophoric polyethers tetronasin and tetronomycin will help to elucidate the mechanisms, which leads to the formation of other tetronate containing natural products like kijanimicin and abyssomycin. The information gained from these experiments will afford the application of the tetronate forming enzymes in the frame of combinatorial biosynthesis. It will permit the incorporation of tetronate forming enzymes into artificial biosynthetic assembly lines to generate novel and more potent agents by directed biosynthesis. Furthermore, all tailoring enzymes, e.g. these arranging for the highly stereoselective ring closures, will find an application in biocatalytic transformations once they were identified. Finally, elucidation of the whole post-PKS steps will help to understand the oddity of nature that created two complex, nearly perfect enantiomers, tetronasin and tetronomycin, which have more or less the same function and mode of action.'