Catalytic mechanism of 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase

Catalytic mechanism of 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) s ynthase (EC 4.1.2.16), an enzyme involved in the biosynthesis of lipopolysa ccharides of Gram-negative bacteria, remains a Fascinating subject for both bioorganic and medicinal researches. The enzyme catalyzes an aldol-type co ndensation of D-arabinose 5-phosphate with phosphoenolpyruvate to produce t he unusual eight-carbon saccharide KDO8P and inorganic phosphate. The struc ture and mechanism of KDO8P synthase have actively studied during last deca de as this enzyme represents an important target for antibiotic therapy. Th is review summarizes the most mechanistically relevant information reported to date, with special emphases on the synthesis and evaluation of a number of analogues of substrates, product and proposed intermediates of the KDO8 P-synthase-catalyzed reaction. The results introduced here illustrate the v alue of organic synthesis to characterize enzymatic reaction. Mechanistic p ostulates have pointed the way to the design of potent inhibitors, and thes e in turn have provided insight into details of the reaction, as well as us eful structural models for elusive intermediates.