mutacin 1140

Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. [1]

The biosynthesis of mutacin 1140 shares some important features with the biosynthesis of other lantibiotic systems; however, there are considerable differences between the biosynthesis of mutacin 1140 and nisin. Mutacin 1140 biosynthesis is a dynamic process in which PTM enzyme modifications and transport are occurring in a highly coordinated fashion, supporting the hypothesis that leader peptide binding at a single locus is sufficient for coordinating PTM enzyme modifications and transport.

Mu1140 analogs were shown to be more effective than currently available treatments for systemic and skin MRSA infections. Further, the study clearly shows that the new analogs are superior to native Mu1140 for the treatment of a systemic MRSA infection.

The four lanthionine rings are labeled A, B, C, and D. The lipid II binding domain consists of rings A and B, while the lateral assembly domain consists of the hinge region (residues 12 to 15) and rings C and D. Protease-susceptible residues Lys and Arg are shown in blue and represent the sites for the alanine substitutions in the Mu1140 analogs. The amino acid abbreviations Dha is dehydroalanine and Dhb is dehydrobutyrine. The labels AlaS and SAla signifying the residues involved in the lanthionine ring formation, AlaS (Dha), AbuS (aminobutyric acid), and SAla (Cys).

[1] MIN JU. Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice.[J]. Frontiers in Microbiology, 2022, 13: 1067410. DOI:10.3389/fmicb.2022.1067410.