Exploring the chemistry of a biological Favorskii rearrangement

The Favorskii rearrangement is named for a reaction in which alpha-halogenated ketones rearrange in the presence of base to form carboxylic acids with loss of halide. Discovered over 100 years ago, this rearrangement involving a cyclopropanone intermediate has since become a standard reaction in synthetic organic chemistry. In 1976 a Favorskii-like rearrangement was first suggested in biology for the biosynthetic rearrangement of a poly-beta-ketone to yield the antibiotic enterocin. Over the past ten years we have explored the biosynthesis and bioengineering of the enterocin polyketides and identified the flavoprotein EncM as the enzyme that single-handedly catalyzes the Favorskii rearrangement that sets-up a series of energetic reactions to yield the multicyclic enterocin nucleus. This seminar will focus on our recent work on the enzymatic mechanism and structural biology of the EncM favorskiiase that involves unusual flavoprotein biochemistry.

J. Piel, C. Hertweck, P. R. Shipley, D. M. Hunt, M. S. Newman, and B. S. Moore, “Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate "Streptomyces maritimus": Evidence for the derailment of an aromatic polyketide synthase”, Chem. Biol., 7, 943-955 (2000).

L. Xiang, J. A. Kalaitzis, and B. S. Moore, “EncM, a versatile enterocin biosynthetic enzyme involved in Favorskii oxidative rearrangement, Aldol condensations, and heterocycle forming reactions”, Proc. Natl. Acad. Sci. USA, 101, 15609-15614 (2004).

Q. Cheng, L. Xiang, M. Izumikawa, D. Meluzzi, and B. S. Moore, “Enzymatic total synthesis of enterocin polyketides”, Nat. Chem. Biol., 3, 557-558 (2007).

For more information contact Mr. Matthew Kennedy (404-894-4016).