Construction and assessment of reaction models of Class I EPSP synthase. Part II: investigation of the EPSP ketal.

Although the proposed mechanisms are reasonable, there are still many questions about the 5-enolpyruvyl shikimate-3-phosphate (EPSP) synthase mechanism that are difficult to answer by experimental means alone. EPSP synthase is a key enzyme in the shikimic acid pathway, which is found only in plants and some micro-organisms and is also molecular target of glyphosate, active component of one of the top-selling herbicides. In the study of reaction mechanism of EPSP synthase, in addition to inorganic phosphate and EPSP products, after long time at equilibrium, it was shown that a side product is formed, the EPSP ketal. In this line, studies using density functional theory (DFT) techniques were performed to investigate the reaction mechanism of formation of EPSP and the corresponding ketal. Our findings indicate some key amino acid residues in the EPSP synthase mechanism and a possible route for the formation of the EPSP ketal.