Mapping the catalytic conformations of an assembly-line polyketide synthase module

Big molecules build small Actinomycete bacteria are prolific producers of bioactive small molecules such as polyketide antibiotics. These molecules are built by the addition of short carbon units to a growing, protein-tethered chain, either iteratively as in fatty acid synthesis or in a modular fashion by a hand-off from one distinct enzyme complex to the next. Bagde et al . and Cogan et al . report structures of polyketide synthase modules in action, taking advantage of antibody stabilization of one of the domains. Both groups visualized multiple conformational states and an asymmetric arrangement of domains, providing insight into how these molecular assembly machines transfer substrates from one active site to another. —MAF