Combinatorial biosynthesis of antimicrobials and other natural products

Combinatorial biosynthesis utilizes the enzymes from antibiotic (and other natural product) biosynthetic pathways to create novel chemical structures. The manipulation of modular polyketide synthases (PKSs) has been the major focus of this effort and has led to the production of, for example, severa l erythromycin analogs. Many new tools for manipulating and studying these multifunctional enzymes have been developed. These include multiple hosts a nd expression systems, enzymology tools for in vitro study, and ways to eng ineer pre-PKS and post-PKS pathways. The result is more rational and faster methods of engineering new compounds for the development of chemotherapeut ic agents from natural products. The most significant recent advances in co mbinatorial biosynthesis are outlined.