Novacta Biosystems Limited

Cantab Anti-Infectives Limited

Michael John Dawson

Jesus Cortes Bargallo

Steven Boakes

Sjoerd Nicolaas Wadman

Antony Nicholas Appleyard

Gabriele Bierbaum

Mona Saadi

Esther Duperchy

Pamela Brown

Brian Arthur Michael Rudd

Anja Hoffmann

Stephanie Schmitz

Provided are compounds, the use of the said compounds in treatment, for example treatment of microbial infections, particularly by Gram negative bacteria. The compounds are polymyxin-based and are represented by the formula (I): 

Compounds

Described are lantibiotic-based compounds, pharmaceutical compositions comprising the same and use of the compounds and said compositions, for the treatment of microbial infection, for exampleorinfection. The lantibiotic-based compounds have antimicrobial activity and in comparison to one or more of actagardine, actagardine B, deoxyactagardine B and deoxyactagardine have retained activity or improved activity.

Actagardine derivatives, and pharmaceutical use thereof

Characterization of the biosynthetic gene cluster for the lantibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine are described.

Lantibiotic biosynthetic gene clusters fromand

A method for the treatment or prophylaxis of a microbial infection of the lower intestine or colon in a subject is described, wherein the method comprises administration to the subject of a type-B lantibiotic, wherein the type-B lantibiotic may include compounds selected from the group consisting of mersacidin, actagardine, plantaricin, planosporicin, ruminococcin, antibiotic 10789, michiganin and haloduracin, and derivatives and variants thereof.

Use of type-B lantibiotic-based compounds having antimicrobial activity

Characterization of the biosynthetic gene cluster for the lantibiotic antibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine, a novel actagardine variant, herein referred to as actagardine B, and variants of both of these produced according to this invention, utilizing genes from the characterized biosynthetic gene clusters, is described.

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The present invention relates to methods and products for improved production of the lantibiotic mersacidin. There is provided a method of producing a mersacidin variant which comprises introducing into a cell which is a &#x394;MrsA host cell an expression vector encoding said variant, and recovering said variant from the cell culture. Preferred variants include the novel variants of Table 1, e.g. mersacidin F3W, said mersacidin F3W optionally having a further one or more variations, e.g. mersacidin F3W G8A. Also provided is acell which is a SigH deficient strain ofsp. HIL Y-85,54728 (NCIMB Accession Number NCIMB 41211); this cell may also be used in the production of mersacidin and its variants. Further aspects of the invention include a DNA cassette which comprises a nucleotide sequence encoding the mersacidin mrsA propeptide, and a method to transform aHIL host cell with plasmid, which method includes the step of electroporation.

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Hertfordshire, United Kingdom

Michael John Dawson