A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters.
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.
LB Genetik, University of Kaiserslautern, Postfach 3049, 67653, Kaiserslautern, Germany.
Antonio
A
Starcevic
Janko
J
Diminic
Jurica
J
Zucko
Mouhsine
M
Elbekali
Tobias
T
Schlosser
Mohamed
M
Lisfi
Ana
A
Vukelic
Paul F
PF
Long
Daslav
D
Hranueli
John
J
Cullum
D005798:Genes, Bacterial; D008957:Models, Genetic; D010453:Peptide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D048630:Polyketide Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics*; D013379:Substrate Specificity
D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase