The leader peptide is essential for the post-translational modification of the DNA-gyrase inhibitor microcin B17.
Microcin B17 (MccB17) is a ribosomally encoded DNA-gyrase inhibitor. Ribosomally encoded antibiotics are derived from precursors containing an N-terminal leader, which is removed during maturation, and a C-terminal structural peptide. PreMccB17, the translational product of mcbA, is modified into proMccB17 by the action of three enzymes, McbB, McbC, and McbD. A chromosomally encoded peptidase then converts proMccB17 into MccB17. The role of McbB, McbC, and McbD is to convert glycine, cysteine, and serine residues present in preMccB17 into four thiazole and four oxazole rings. Using a modification-specific antibody rather than antimicrobial activity, we show that the 26-amino-acid N-terminal leader of preMccB17 is essential for the conversion of preMccB17 into proMccB17. Neither a preMccB17 peptide lacking the leader nor a preMccB17-beta-galactosidase fusion lacking the leader are post-translationally modified.
Madison
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LL
Department of Molecular Genetics and Microbiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Vivas
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EI
Li
Y M
YM
Walsh
C T
CT
Kolter
R
R
D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D016296:Mutagenesis; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D001430:Bacteriocins; D004791:Enzyme Inhibitors; D011498:Protein Precursors; D021382:Protein Sorting Signals; D059005:Topoisomerase II Inhibitors; C020411:microcin