A unique reaction in a common pathway: mechanism and function of chorismate synthase in the shikimate pathway

Chorismate synthase, the seventh enzyme in the shikimate pathway, catalyzes the transformation of 5-enolpyruvylshikimate 3-phosphate to chorismate whi ch is the last common precursor in the biosynthesis of numerous aromatic co mpounds in bacteria, fungi and plants. The enzyme has an absolute requireme nt for reduced FMN as a cofactor, although the 1,4-anti elimination of phos phate and the C(6proR)-hydrogen does not involve a net redox change. The ro le of the reduced FMN in catalysis has long been elusive. However, recent d etailed kinetic and bioorganic approaches have fundamentally advanced our u nderstanding of the mechanism of action, suggesting an initial electron tra nsfer from tightly bound reduced flavin to the substrate, a process which r esults in C-O bond cleavage. Studies on chorismate synthases from bacteria, fungi and plants revealed that in these organisms the reduced FMN cofactor is made available in different ways to chorismate synthase: chorismate syn thases in fungi - in contrast to those in bacteria and plants - carry a sec ond enzymatic activity which enables them to reduce FMN at the expense of N ADPH. Yet, as shown by the analysis of the corresponding genes, all chorism ate synthases are derived from a common ancestor. However, several issues r evolving around the origin of reduced FMN, as well as the possible regulati on of the enzyme activity by means of the availability of reduced FMN, rema in poorly understood. This review summarizes recent developments in the bio chemical and genetic arena and identifies future aims in this field.