Thursday, August 2, 2007 - 3:35 PM
S182
Engineered biosynthesis of lantibiotics, production of novel mersacidins in Bacillus
Jesus Cortes, Novacta Biosystems Limited, UH Innovation Centre, College Lane, Hatfield, United Kingdom
Mersacidin is a tetracyclic lantibiotic with in vitro and in vivo antibacterial activity against Gram-positive pathogens. In order to probe the specificity of the biosynthetic pathway of mersacidin and obtain analogues with improved antibacterial activity, an efficient system for generation of variants of this lantibiotic was developed. A saturation mutagenesis library of the residues of mersacidin not involved in cycle formation was constructed and used to validate this system. Mersacidin analogues were obtained in 35% of the cases, producing a collection of 80 new compounds. This system was used for the production of deletion and insertion mutants of mersacidin, the outcome of these libraries suggests that this system can be extended for production of mersacidin variants with multiple changes that will allow a full investigation of the potential use of modified mersacidins as therapeutic agents. Insights of the biosynthetic pathway of mersacidin and antibacterial properties of the new analogues are discussed.
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See more of The Annual Meeting and Exhibition 2007 (July 29 - August 2, 2007)
See more of Invited Oral Papers
See more of The Annual Meeting and Exhibition 2007 (July 29 - August 2, 2007)