Wednesday, July 29, 2009 - 10:30 AM
S108

Metabolic engineering of lantibiotics

Michael J. Dawson and Jesus Cortes Bargallo. Novacta Biosystems Limited, BioPark Hertfordshire, Broadwater Road, Welwyn Garden City, United Kingdom

Lantibiotics are highly post-translationally modified peptides produced by Gram-positive bacteria. Due to the rise in antibiotic resistance there has been recent interest in developing lantibiotics as antibacterial agents. For complex microbial secondary metabolites manipulation of the biosynthetic pathways is a powerful means of generating analogues to optimise activity and other pharmaceutical properties. Being ribosomally-derived peptides in origin, the lantibiotics are particularly amenable to this approach.

Although metabolic pathway engineering for manipulation of secondary metabolite structure has been used extensively as a laboratory tool only relatively few examples have become industrially important partly because the methods have not been applicable to generation of large numbers of analogues in a parallel fashion or because changes have led to much reduced yields of the target molecules.

The presentation will review the pros and cons of different approaches which have been used for the genetic manipulation of lantibiotic structure and will introduce high throughput methods for structural modification. The consequence of structural changes on lantibiotic yields will also be addressed.