Obiettivo
The focus of this proposal is to develop an economically viable production process for the lantibiotic NAI-107, a new antibiotic with the potential to treat life-threatening infections caused by multidrug-resistant Gram-positive pathogens. NAI-107 is produced by fermentation of the actinomycete Microbispora sp., is undergoing formal toxicology studies and is expected to enter Phase I clinical trials in the second half of 2009. NAICONS, an SME participating in the project and acting as coordinator, is developing NAI-107. A challenge in advancing a new antibiotic into clinical development is to devise a production process that will deliver a high quality compound at reasonable yields. This is particularly relevant for NAI-107 since no lantibiotics are industrially produced as drugs for human use and there are no examples of industrial use of Microbispora. The development of a robust and economically feasible production process for NAI-107 requires the integration of basic knowledge of the physiology of the strain which can be best obtained by a combination of classical and post-genomic approaches (proteome/transcriptome), with a detailed knowledge of the production process and its scalability to industrial level. This will be achieved by flux analyses and 2D-maps for discovering primary metabolism proteins up-regulated during antibiotic production. Combined with a study of other limiting steps, such as precursor uptake, product excretion and the intrinsic resistance of the producing strain, and with analysis of the transcriptional regulation of the NAI-107 biosynthetic genes, bottlenecks in production will be identified and bypassed by metabolic engineering leading to an optimized metabolic pathway for the production of this life-saving antibiotic and an efficient production process utilizing a high producing strain, an improved production medium and an efficient recovery process.
Campo scientifico
- engineering and technologyindustrial biotechnologymetabolic engineering
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- medical and health sciencesbasic medicinephysiology
- medical and health sciencesbasic medicinetoxicology
- engineering and technologyindustrial biotechnologybioprocessing technologiesfermentation
Invito a presentare proposte
FP7-KBBE-2009-3
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Meccanismo di finanziamento
CP-FP - Small or medium-scale focused research projectCoordinatore
20138 Milano
Italia