American Chemical Society
jm6b00219_si_001.pdf (20.93 MB)

Total Synthesis of Laspartomycin C and Characterization of Its Antibacterial Mechanism of Action

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journal contribution
posted on 2016-03-11, 00:00 authored by Laurens H. J. Kleijn, Sabine F. Oppedijk, Peter ’t Hart, Roel M. van Harten, Leah A. Martin-Visscher, Johan Kemmink, Eefjan Breukink, Nathaniel I. Martin
Laspartomycin C is a lipopeptide antibiotic with activity against a range of Gram-positive bacteria including drug-resistant pathogens. We report the first total synthesis of laspartomycin C as well as a series of structural variants. Laspartomycin C was found to specifically bind undecaprenyl phosphate (C55-P) and inhibit formation of the bacterial cell wall precursor lipid II. While several clinically used antibiotics target the lipid II pathway, there are no approved drugs that act on its C55-P precursor.