Computer modelling of recombination between modular biosynthesis clusters

Modular clusters for the biosynthesis of polyketides (PKS) and non-ribosomal peptide synthesis (NRPS) are common and include many commercially important products. Each step of the biosynthesis is encoded by a different module, which are usually present on several polypeptides. It is likely that the observed diversity of clusters has evolved by processes including homologous recombination and the generation of novel clusters by homologous recombination is a potential route to novel chemical structures. A BLAST algorithm was used to model recombination by selection of sites of local similarity. This showed many potential recombination sites in the PKS clusters, which were mostly present in the ketosynthase domains of the modules. A range of BLAST parameters was used and it was shown that the prediction of the modules that recombine was not very sensitive to changes in stringency. The modules could be grouped into several discrete classes on the basis of their predicted recombination partners. A program was also written to predict the linear backbone structure of the novel polyketides produced by the recombinant clusters. In contrast to the PKS clusters, the NRPS clusters did not show many potential recombination sites.