The dependence of polyketide synthase and terpene cyclase mechanistic adaptation on the chemistry of their oligomeric substrates illuminates a convergent evolutionary strategy for shaping cyclization in these otherwise disparate reactions. Evolution of these enzyme families relies on rhythmic tangos, in which the enzymes and substrates together determine product outcome by negotiating decision networks governing intrinsic and induced chemical reactivities.

Austin MB, O’Maille PE, Noel JP.

Michael B. Austin, Paul E. O’Maille and Joseph P. Noel are in the Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Jack H. Skirball Center for Chemical Biology and Proteomics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. noel@salk.edu.