New Chorismate Metabolic Pathway | Chemical & Engineering News
Volume 86 Issue 2 | p. 36 | Concentrates
Issue Date: January 14, 2008

New Chorismate Metabolic Pathway

Department: Science & Technology
News Channels: JACS In C&EN

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.

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