P12: Mining for active strains in a large strain library

Monday, November 7, 2011
Capri Ballroom (Marriott Marco Island)
Paolo Monciardini1, Margherita Sosio2, Stefania Serina1, Sonia Maffioli2, Eleonora Gaspari3, Cristina Brunati3, Paola Guglierame3, Ambrogina Guindani1 and Stefano Donadio2, (1)KtedoGen, Milano, Italy, (2)NAICONS, Milano, Italy, (3)NeED Pharma, Milano, Italy
NAICONS’ strain collection comprises over 65,000 strains, mainly filamentous actinomycetes and filamentous fungi. The library was constructed with an emphasis on the isolation of uncommon strains, and contains several members of Actinomycetales genera which are under-represented in public culture collections. It is one of the largest and most diversified strain collections available. Traditionally, the strains were grown under different conditions, generating >160,000 extracts from the corresponding fermentation broths, which were employed in several high throughput screening programs. All data generated from the screening programs were acquired in the NPL database, which records also strains and methods for extract preparation. While the main emphasis of the screening was on antimicrobial targets, only a small fraction of the active extracts were characterized up to the identification of the active compounds. Nonetheless, several novel molecules with antibacterial properties were identified among the characterized compounds. We have analyzed the NPL database, identifying extracts that showed activity in growth inhibition assays against Gram-positive bacteria, Gram-negative bacteria or fungi, and prioritizing and cataloguing the corresponding strains from the library. Pilot experiments have been performed, re-growing and processing randomly selected strains. The newly generated extracts confirm the historical activity for >60% of the strains. These results indicate that specific subsets of strains, selected by in silico screening, can yield extracts highly enriched in the desired bioactivity. This enrichment procedure allows focused screening campaigns on a limited number of strains.
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