EVIDENCE FOR A DOUBLE-HELICAL STRUCTURE FOR MODULAR POLYKETIDE SYNTHASES

Modular polyketide synthases are multienzymes responsible for the bios ynthesis of a large number of clinically important natural products. T hey contain multiple sets, or modules, of enzymatic activities, distri buted between a few giant multienzymes and there is one module for eve ry successive cycle of polyketide chain extension. We show here that e ach multienzyme in a typical modular polyketide synthase forms a (poss ibly helical) parallel dimer, and that each pair of identical modules interacts closely across the dimer interface. Such an arrangement woul d allow identical modules to share active sites for chain extension, a nd thus to function independently of flanking modules, which would hav e important implications both for mechanisms of evolution of polyketid e synthases and for their future genetic engineering.