The Acceptor for Polar Head Groups of the Lipid A Component of Salmonella Lipopolysaccharides

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Abstract
Experiments which determine at which stage in the lipid A biosynthesis the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid are transferred to the diphosphorylated glucosamine backbone of the lipid A structure were described. Use was made of a conditional lethal mutant of S. typhimurium (Ts1) which is defective in the synthesis of 3-deoxy-D-manno-octulosonic acid 8-phospahte and accumulates under nonpermissive conditions an underacylated lipid A intermediate. Pulse-chase experiments, including a detailed analysis of radioactive pulse and chase products, demonstrated that this underacylated compound is a key intermediate in the lipid A synthesis. It can serve as direct acceptor for the incorporation of the polar head groups 4-aminoarabinose, phosphorylethanolamine and 3-deoxy-D-manno-octulosonic acid. On the basis of these findings some steps in the sequence of reactions involved in the lipid A biosynthesis are proposed.