Categories: General
      Date: Nov 24, 2010
     Title: Recombination paper published

A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters.

J. Ind. Microbiol. Biotechnol. Published online: 24 November 2010
DOI 10.1007/s10295-010-0909-0

Antonio Starcevic, Janko Diminic, Jurica Zucko, Mouhsine Elbekali, Tobias Schlosser, Mohamed Lisfi, Ana Vukelic, Paul F. Long, Daslav Hranueli and John Cullum

LB Genetik, University of Kaiserslautern, Postfach 3049, 67653 Kaiserslautern, Germany

Section for Bioinformatics, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia
Section for Mathematics, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia

Pharmaceutical Science Institute, King’s College London, Franklin-Wilkins Building, Stamford Street, London, SE1 9NH, UK

An in silico model for homoeologous recombination between gene clusters encoding modular polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) was developed. This model was used to analyze recombination between 12 PKS clusters from Streptomyces species and related genera to predict if new clusters might give rise to new products. In many cases, there were only a limited number of recombination sites (about 13 per cluster pair), suggesting that recombination may pose constraints on the evolution of PKS clusters. Most recombination events occurred between pairs of ketosynthase (KS) domains, allowing the biosynthetic outcome of the recombinant modules to be predicted. About 30% of recombinants were predicted to produce polyketides. Four NRPS clusters from Streptomyces strains were also used for in silico recombination. They yielded a comparable number of recombinants to PKS clusters, but the adenylation (A) domains contained the largest proportion of recombination events; this might be a mechanism for producing new substrate specificities. The extreme G + C-content, the presence of linear chromosomes and plasmids, as well as the lack of a mutSL-mismatch repair system should favor production of recombinants in Streptomyces species.