Obiettivo The aim of the project is to generate novel hybrid molecules, potentially showing anti-tumour activity, by engineering several pathways involved in the biosynthesis of anti-tumour drugs by streptomycetes. The target drugs for engineering will be the angucyclines (urdamycins), the aureolic acid group (mithramycin, chromomycin and olivomycin), the anthracyclines group and elloramycin and tetracenomycin. Gene clusters (or specific genes) involved in the biosynthesis of these anti-tumour drugs will be isolated and sequenced to identify potential gene functions and they will be used for interspecific exchange experiments to create new hybrid gene constructions. Novel molecules synthesised by these clones will be identified, isolated and their structures elucidated. Mutants blocked at specific steps of the biosynthesis will be also generated by gene replacement techniques and the accumulated products isolated and structurally identified. These accumulated products will be used for directed biosynthesis of specific strains or mutants to generate new compounds. Gene clusters will be also introduced into a streptomycete strain able to synthesise fluoroacetate such that fluoroacetate may be used as starter unit to generate modified molecules. In addition, new molecules will be also generated by feeding specific strains with compounds derived from polyketide model systems. Potential cytostatic activity of the novel molecules will be assayed using different tumour cell lines. The experimental approach used in this proposal will be a co-ordinated, multi-disciplinary study using molecular biology, organic chemistry and cell cultures and will involve five university research groups and two small/medium sized enterprises. Achievements of the goal of the project will have important biotechnological implications and could directly benefit the european pharmaceutical sector interested in anti-tumour drugs. Campo scientifico natural scienceschemical sciencesorganic chemistrynatural sciencesbiological sciencesmolecular biology Programma(i) FP4-BIOTECH 2 - Specific research, technological development and demonstration programme in the field of biotechnology, 1994-1998 Argomento(i) 010101 - Microbial factories Invito a presentare proposte Data not available Meccanismo di finanziamento CSC - Cost-sharing contracts Coordinatore UNIVERSIDAD DE OVIEDO Contributo UE Nessun dato Indirizzo S/N,Julian Claveria s/n 33006 Oviedo Spagna Mostra sulla mappa Costo totale Nessun dato Partecipanti (6) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto Analyticon Gesellschaft für Chemische Analytik und Consulting GmbH Germania Contributo UE Nessun dato Indirizzo 25,Gustav-Meyer-Allee 13355 Berlin Mostra sulla mappa Costo totale Nessun dato Eberhard-Karls-Universität Tübingen Germania Contributo UE Nessun dato Indirizzo Auf der Morgenstelle 28 72076 Tübingen Mostra sulla mappa Costo totale Nessun dato GALILAEUS OY Finlandia Contributo UE Nessun dato Indirizzo Kairiskulmantie 10 KAARINA Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato Georg-August-Universität Göttingen Germania Contributo UE Nessun dato Indirizzo 2,Tammannstrasse 37077 Göttingen Mostra sulla mappa Costo totale Nessun dato UNIVERSITY OF DURHAM Regno Unito Contributo UE Nessun dato Indirizzo South Road, Science Laboratories DH1 3LE DURHAM Mostra sulla mappa Costo totale Nessun dato UNIVERSITY OF TURKU Finlandia Contributo UE Nessun dato Indirizzo Vatselankatu 2 20014 TURKU / ABO Mostra sulla mappa Costo totale Nessun dato
