9.A.52 The Microcin J25 (Microsin J25) Family

Microcin J25 (MccJ25) is a cyclic peptide of 21 unmodified amino acis residues produced by a fecal strain of Escherichia coli. It is mainly directed to Enterobacteriaceae, including several pathogenic E. coli, Salmonella and Shigella strains. Rintoul et al., 2001 showed that MccJ25 acts on the cytoplasmic membrane of Salmonella newport cells producing alterations of the membrane permeability, and subsequent ion gradient dissipation. This initiates the growth inhibition process. This suggest that the disruption of the cytoplasmic memrbane gradient is closely related to the bactericidal activity of MccJ25.The structures of Microcin J25 is known (1S7P_A; 5T56-A-D).

Lasso peptides exist naturally in a threaded state as rotaxanes, and can be cleaved in their loop regions to serve as building blocks for catenanes. Mutagenesis of the lasso peptide microcin J25 (MccJ25) with two cysteine residues followed by cleavage of the peptide with trypsin led to a [1]rotaxane structure that self-assembled into a [3]catenane and [4]catenanes in aqueous solution. The [3]catenane represents the smallest ring size of a catenane composed solely of polypeptide segments. The NMR structure of the [3]catenane was determined, suggesting that burial of hydrophobic residues may be a driving force for assembly of the catenane structure (Allen and Link 2016).

The reaction probably catalyzed by MccJ25 is:

cations (in) ⇌ cations (out)



Allen, C.D. and A.J. Link. (2016). Self-Assembly of Catenanes from Lasso Peptides. J. Am. Chem. Soc. 138: 14214-14217.

Braffman, N.R., F.J. Piscotta, J. Hauver, E.A. Campbell, A.J. Link, and S.A. Darst. (2019). Structural mechanism of transcription inhibition by lasso peptides microcin J25 and capistruin. Proc. Natl. Acad. Sci. USA 116: 1273-1278.

Mukhopadhyay, J., E. Sineva, J. Knight, R.M. Levy, and R.H. Ebright. (2004). Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol. Cell 14: 739-751.

Rintoul, M.R., B.F. de Arcuri, R.A. Salomón, R.N. Farías, and R.D. Morero. (2001). The antibacterial action of microcin J25: evidence for disruption of cytoplasmic membrane energization in Salmonella newport. FEMS Microbiol. Lett. 204: 265-270.

Socias, S.B., K. Severinov, and R.A. Salomon. (2009). The Ile13 residue of microcin J25 is essential for recognition by the receptor FhuA, but not by the inner membrane transporter SbmA. FEMS Microbiol. Lett. 301: 124-129.


TC#NameOrganismal TypeExample

Microcin J25 (MccJ25) cyclic 21 aa peptide, derived from a precursor of 58 aas. The Ile13 residue of microcin J25 is essential for recognition by the receptor FhuA, but not by the inner membrane transporter SbmA (Socias et al., 2009). It inhibits transcription by binding deep within RNAP secondary channel, where it sterically blocks the folding of the trigger loop, which is essential for efficient catalysis (Mukhopadhyay et al. 2004; Braffman et al. 2019). It also acts on the cytoplasmic membrane of Salmonella newport, producing alteration of membrane permeability and subsequent gradient dissipation, which inhibits several processes essential for cell viability, such as oxygen consumption (Rintoul et al. 2001).


Microcin J25 of E. coli (Q9X2V7)