In the Mar 31 issue of the Proceedings of the National Academy of Sciences, Prof. Sheryl Tsai, former graduate student Tyler Korman and undergraduate student Justin Wong, in collaboration with the Townsend lab in the Johns Hopkins University, reported the structural and chemical biology study of the aflatoxin polyketide synthase thioesterase domain (PksA TE) which, instead of catalyzing the C-O bond formation/hydrolysis reaction characteristic of a TE, promotes the C-C bond forming Claisen cyclization. The crystal structure of PksA TE revealed its unusual water-excluding binding pocket that promotes its cyclization activity. The study affords the first mechanistic insights into the C-C bond-forming TEs widely distributed in fungi.