Modifying the Lantibiotic Mutacin 1140 for Increased Yield, Activity, and Stability

Applied and Environmental Microbiology
Mengxin Geng, Leif Smith

Abstract

Mutacin 1140 belongs to the epidermin family of type AI lantibiotics. This family has a broad spectrum of activity against Gram-positive bacteria. The binding of mutacin 1140 to lipid II leads to the inhibition of cell wall synthesis. Pharmacokinetic experiments with type AI lantibiotics are generally discouraging for clinical applications due to the short half-life of these compounds. The unprotected dehydrated and protease-susceptible residues outside the lanthionine rings may play a role in the short half-life in physiological settings. Previous mutagenesis work on mutacin 1140 has been limited to the lanthionine-forming residues, the C-terminally decarboxylated residue, and single amino acid substitutions at residues Phe1, Trp4, Dha5, and Arg13. To study the importance of the dehydrated (Dha5 and Dhb14) and protease-susceptible (Lys2 and Arg13) residues within mutacin 1140 for stability and bioactivity, each of these residues was evaluated for its impact on production and inhibitory activity. More than 15 analogs were purified, enabling direct comparison of the activities against a select panel of Gram-positive bacteria. The efficiency of the posttranslational modification (PTM) machinery of mutacin 1140 is highly restricte...Continue Reading

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Citations

Jul 17, 2018·Chemical Biology & Drug Design·Johan A KersMartin Handfield
May 31, 2019·Physical Chemistry Chemical Physics : PCCP·Rudramani PokhrelPrem P Chapagain
Aug 23, 2019·World Journal of Microbiology & Biotechnology·Vasundhera GuptaSuresh Korpole
Apr 2, 2020·Journal of Bacteriology·Delphine DufourCéline M Lévesque
Dec 1, 2020·Frontiers in Microbiology·Hamid Reza Karbalaei-Heidari, Nediljko Budisa
Nov 2, 2021·Journal of the American Chemical Society·Tung LeWilfred A van der Donk

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