A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters
- 241 Downloads
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.
KeywordsPolyketide synthase Non-ribosomal peptide synthetase Streptomyces Bacillus Chi sequence
- 5.Brautaset T, Sekurova ON, Sletta H, Ellingsen TE, Strøm AR, Valla S, Zotchev SB (2000) Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chem Biol 7:395–403PubMedCrossRefGoogle Scholar
- 7.Caboche S, Pupin M, Leclère V, Fontaine A, Jacques P, Kucherov G (2008) NORINE: a database of nonribosomal peptides. Nucleic Acids Res 36(Database issue):D326–D331Google Scholar
- 12.Denapaite D, Paravić Radičević A, Čajavec B, Hunter IS, Hranueli D, Cullum J (2005) Persistence of the chromosome end regions at low copy number in mutant strains of Streptomyces rimosus and S. lividans. Food Technol Biotechnol 43:9–17Google Scholar
- 38.Zucko J, Starcevic A, Diminic J, Elbekali M, Lisfi M, Long PF, Cullum J, Hranueli D (2010) From DNA sequences to chemical structures—methods for mining microbial genomic and metagenomic datasets for new natural products. Food Technol Biotechnol 48:234–242Google Scholar