New Chorismate Metabolic Pathway

At least six bacterial biosynthetic routes to key biomolecules—including several amino acids, the vitamin folate, and the coenzyme ubiquinone—begin with the key metabolic intermediate chorismate. Researchers have now identified a seventh branching point in chorismate metabolism and determined that a product of this pathway is a major component of the enediyne antitumor antibiotic C-1027, one of the most cytotoxic natural products known (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0708750105). Ben Shen and coworkers at the University of Wisconsin, Madison, show that the benzoxazolinate moiety of C-1027 is derived from chorismate by the sequential action of two enzymes: SgcD, a 2-amino-2-deoxyisochorismate (ADIC) synthase, and SgcG, an ADIC dehydrogenase. The reactions catalyzed by these enzymes yield 3-enolpyruvoylanthranilate, an intermediate that is further modified to form C-1027's benzoxazolinate group. The findings could "provide the inspiration to search for other variations of chorismate-using enzymes" and could facilitate "genetic engineering and combinatorial biosynthetic approaches aimed at harnessing the inherent power of the C-1027 scaffold," the researchers write.