Autoinduction Specificities of the Lantibiotics Subtilin and Nisin.
The biosynthesis of the lantibiotics subtilin and nisin is regulated by autoinduction via two-component systems. Although subtilin is structurally closely related to nisin and contains the same lanthionine ring structure, both lantibiotics specifically autoinduce their biosynthesis. Subtilin and also the subtilin-like lantibiotics entianin and ericin autoinduce the two-component system SpaRK of Bacillus subtilis, whereas the biosynthesis of nisin is autoinduced via the two-component system NisRK of Lactococcus lactis. Autoinduction is highly specific for the respective lantibiotic and therefore of major importance for the functional expression of genetically engineered subtilin-like lantibiotics. To identify the structural features required for subtilin autoinduction, subtilin-nisin hybrids and specific point mutations of amino acid position 1 were generated. For subtilin autoinduction, the N-terminal tryptophan is the most important for full SpaK activation. The failure of subtilin to autoinduce the histidine kinase NisK mainly depends on the N-terminal tryptophan, as its single exchange to the aliphatic amino acid residues isoleucine, leucine, and valine provided NisK autoinduction. In addition, the production of subtilin variants which did not autoinduce their own biosynthesis could be rescued upon heterologous coexpression in B. subtilis DSM15029 by the autoinducing subtilin-like lantibiotic entianin.
Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany.
Tobias
T
Spieß
Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany.
Sophie Marianne
SM
Korn
Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany koetter@bio.uni-frankfurt.de entian@bio.uni-frankfurt.de.
Peter
P
Kötter
Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany koetter@bio.uni-frankfurt.de entian@bio.uni-frankfurt.de.
Karl-Dieter
KD
Entian
D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001430:Bacteriocins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D009561:Nisin / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D001430:Bacteriocins; D009561:Nisin; C102526:nisin A; C002836:subtilin