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9.A.52 The Lasso Peptide 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).

There are several lasso peptides, all of similar size and general characteristics.  These have not all been shown to affect bacterial membrane permeability, but many of them are antimicrobial. Although homology has not been established, some similarity in their primary amino acid sequences has been noted.  These peptides are listed in this family (Carson et al. 2023).

The reaction probably catalyzed by MccJ25 is:

cations (in) ⇌ cations (out)


References associated with 9.A.52 family:

Allen, C.D. and A.J. Link. (2016). Self-Assembly of Catenanes from Lasso Peptides. J. Am. Chem. Soc. 138: 14214-14217. 27768305
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. 30626643
Carson, D.V., M. Patiño, H.E. Elashal, A.J. Cartagena, Y. Zhang, M.E. Whitley, L. So, A.K. Kayser-Browne, A.M. Earl, R.P. Bhattacharyya, and A.J. Link. (2023). Cloacaenodin, an Antimicrobial Lasso Peptide with Activity against. ACS Infect Dis 9: 111-121. 36519726
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. 15200952
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. 11731133
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. 19843311