Heterologous expression and engineering studies of labyrinthopeptins, class III lantibiotics from Actinomadura namibiensis.
Labyrinthopeptins are class III lantibiotics produced by the actinomycete Actinomadura namibiensis. The most characteristic structural feature is the posttranslationally installed triamino triacid labionin with a quaternary α-carbon. In addition to the unique structure, labyrinthopeptin A2 possess remarkable antiviral and antiallodynic biological activities. To harness the substrate tolerance of the biosynthetic machinery, we developed an efficient system for the generation of labyrinthopeptin analogs. Streptomyces lividans was used as a heterologous host since the natural producer Actinomadura namibiensis remained genetically intractable. Generation of a library of 39 mutants allowed identification of variable and invariable regions in the labyrinthopeptin structures. Additional data on the flexibility of the biosynthetic machinery were provided by in vitro experiments. This study is detailed investigation on the potential to generate analogs of class III lantibiotics by genetic engineering.
Institut für Chemie, Technische Universität Berlin, 10623 Berlin, Germany.
Joanna M
JM
Krawczyk
Ginka H
GH
Völler
Bartlomiej
B
Krawczyk
Julian
J
Kretz
Mark
M
Brönstrup
Roderich D
RD
Süssmuth
D039903:Actinobacteria / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001430:Bacteriocins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D005813:Genes, Synthetic; D006868:Hydrolysis; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D048170:Streptomyces lividans / Q000235:genetics / Q000378:metabolism
D001430:Bacteriocins; C582102:labyrinthopeptin A1, Actinomadura namibiensis; C550284:labyrinthopeptin A2