Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility

Moving modules drive biosynthesis Modular biosynthesis of small molecules—where enzyme units can be swapped in and out of assembly line complexes to produce desired products—is a distant goal in the lab despite a huge diversity of modular systems in nature. Part of the challenge is in understanding how modules interact and hand off intermediates. Reimer et al. determined crystal structures of portions of a nonribosomal peptide synthetase, including a full dimodule. Module positioning differed between these structures even when the same intermediate was attached to the enzyme. The authors used small-angle x-ray scattering to confirm that large conformational changes are possible during biosynthesis and handoff between modules. Science , this issue p. eaaw4388