Combinatorial polyketide biosynthesis at higher stage

Mol Syst Biol. 1: 2005.0025Modular polyketide synthases (PKS) of bacteria provide an amazing molecular assembly line for the biosynthesis of complex polyketides. This biosynthesis system has, since its discovery, attracted the attention of scientists and pharmaceutical companies owing to its combinatorial potential. It has provoked the idea of constructing ‘unnatural’ product libraries containing a myriad of compounds with all possible lengths and combinations of carbon units. The recent study by Menzella et al (2005) represents an important milestone on the way to construct such libraries, and highlights both the potential and the limits of biocombinatorial strategies for a complete reorganisation of natural enzyme units. The group at Kosan Biosciences Inc. has adopted and improved existing engineering techniques and describes for the first time a high‐throughput methodology for the generation of synthetic triketides.Natural polyketides derived from giant PKS complexes were mostly isolated from microbes in the soil, but were increasingly discovered also in the oceans and have served as lead products for some of the most important pharmaceuticals currently on the market (Staunton and Weissman, 2001). They include antibiotics (e.g. erythromycin A), anticancer drugs (e.g. …