Abstract
The gene cluster encoding biosynthesis of the polyketide backbone of erythromycin is organised as repeated modules of functional domains. The similarity of the domain arrangements among the complex polyketide natural products provides a strategy to generate an array of different structures using a combinatorial approach. More than fifty 6-deoxyerythronolide B (6dEB) analogs were obtained by substitution of catalytic domains via single, double and triple alterations. This genetic manipulation approach to engineer such molecules, which would otherwise be impractical to produce by chemical methods, is very challenging and promising for the development of novel polyketides that could have utility in pharmaceutical applications in the future.
