Peptidoglycan (PGN) is an essential component of the bacterial cell, which maintains cell shape and protects bacteria from internal osmotic pressure. The last stage of biosynthesis of bacterial PGN begins with polymerization of the building block, Lipid II, and subsequently cross-linking to form net-like mature PGN catalyzed by penicillin-binding proteins. The amphipathic Lipid II is synthesized in the cytosol then translocated across the cytoplasmic membrane to the exterior surface of the cell by a puzzling enzyme “flippase” through a unclear protein machinery. Recently, in vivo studies concluded that MurJ is an essential enzyme to play as a flippase responding for Lipid II translocation in E coli. Herein, we synthesized a series of NBD-Lipid II analogues were prepared via bio-catalytic or chemical approach with modification of lipid, peptide, or sugar moiety and developed an “out-to-in” liposome-based in vitro functional assay to evaluate substrate activities against E coli. MurJ (MurJEC). Based on these results, substrate-inspired inhibitor design and inhibitor screening will be investigated.

Development and study of the substrate specificities of lipid II analogues against MurJ flippase via an in virto liposome-based assay

254th National Meeting (2017)

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