Lipopolysaccharides (LPS) are large molecules that anchored in the outer membrane of Gram-negative bacteria by lipid A, to which a non-repeating core oligosaccharide and a distal polysaccharide termed O-antigen are attached.  LPS contributes to the integrity of OM and protects the cells against various environmental stress including lipophilic antibiotics and host immune system.  Our chemical biology exploration of LPS involves the total synthesis of a variety of LPS through combination of chemical and enzymatic approaches.   We have successfully developed a chemo-enzymatic approach to synthesize the repeating O-epitope unit (lipid linked oligosaccharide) <i>in vitro</i> by using the biosynthetic glycosyltransferases.  Subsequently, we successfully defined the function of Wzz and Wzy, which are the two key enzymes involved in the polymerization of the O-epitope unit.   Updated results will be presented for the chemo-enzymatic synthesis of the lipid A linked inner core and out cores of LPS.  Finally, enzyme WaaL is being used to add the repeated O-polysaccharide to the core of LPS to produce full synthetic LPS.   The platform of synthetic LPS will give a comprehensive understanding of the biosynthetic mechanism and structure-activity relationship (SAR) of LPS for biological investigation and for pharmaceutical development against infectious diseases.<br/><br/>

Chemical biology approach to explore biosynthesis and biogenesis of lipopolysaccharides

253rd National Meeting (2017)

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