A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters |
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Authors: | Antonio Starcevic Janko Diminic Jurica Zucko Mouhsine Elbekali Tobias Schlosser Mohamed Lisfi Ana Vukelic Paul F Long Daslav Hranueli John Cullum |
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Institution: | (1) LB Genetik, University of Kaiserslautern, Postfach 3049, 67653 Kaiserslautern, Germany;(2) Section for Bioinformatics, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia;(3) Section for Mathematics, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia;(4) Pharmaceutical Science Institute, King’s College London, Franklin-Wilkins Building, Stamford Street, London, SE1 9NH, UK |
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Abstract: | 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. |
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