Microcins: New peptide antibiotics of enterobacteria and genetic control of their synthesis

Screening of a large number of isolates of enterobacteria resulted in the isolation of Escherichia coli strains actively producing type B and C microcins. The synthesis of microcins and the immunity toward them is usually ensured by plasmids. The plasmid genes responsible for the synthesis of three microcins and the immune response to them were cloned and mapped. High conservation of the genes determining the synthesis of three type B microcins whose producers had been isolated in geographically distant areas was demonstrated. We and elucidated the structure of a new microcin C51 found by us, a highly active antibiotic with the broadest activity spectrum among known microcins. This antibiotic is a nucleopeptide of 1.18 kDa; it contains a heptapeptide with an N-terminal formylmethionine and a C-terminal asparagine that is linked with AMP through a phosphoramide bond. It was shown that four plasmid genes in a single operon are responsible for the production of microcin C51, and one gene for the immune response to the microcin. In the course of the biosynthesis of microcin C51, ribosomal synthesis of the microcin heptapeptide encoded by a small gene (21 bp) is followed by posttranslational modification. In experiments with the cloned promoter of the microcin operon it was shown that transcription from this promoter was activated when the growth of the culture slowed down and it entered the stationary phase. A characteristic feature of the transcription regulation is its dependence on the RNA polymerase σ^s subunit.