Manipulating the regulatory genes for teicoplanin production in Actinoplanes teichomyceticus

Actinoplanes teichomyceticus produces the lipoglycopeptide antibiotic teicoplanin, which is considered a last line of defense against multidrug resistant Gram-positive cocci. Different strategies have been employed to generate industrial producers of teicoplanin, however they do not include manipulations of teicoplanin biosynthetic genes due to a poorly developed genetic toolkit for this strain. Through this work, we extend the choice of vectors that can be conjugally transferred and maintained in A. teichomyceticus. Antibiotic producing properties and stability of the transconjugants have been examined. As an illustration of the utility of pSG5-based vector pKC1139, we improved teicoplanin production by the wild type strain via manipulations of two regulatory genes from the teicoplanin biosynthetic cluster, tcp28 and tcp29.