Metabolic and evolutionary insights into the closely-related species Streptomyces coelicolor and Streptomyces lividans deduced from high-resolution comparative genomic hybridization

Abstract

BackgroundWhilst being closely related to the model actinomycete Streptomyces coelicolor A3(2), S. lividans 66 differs from it in several significant and phenotypically observable ways, including antibiotic production. Previous comparative gene hybridization studies investigating such differences have used low-density (one probe per gene) PCR-based spotted arrays. Here we use new experimentally optimised 104,000 × 60-mer probe arrays to characterize in detail the genomic differences between wild-type S. lividans 66, a derivative industrial strain, TK24, and S. coelicolor M145.ResultsThe high coverage and specificity (detection of three nucleotide differences) of the new microarrays used has highlighted the macroscopic genomic differences between two S. lividans strains and S. coelicolor. In a series of case studies we have validated the microarray and have identified subtle changes in genomic structure which occur in the Asp-activating adenylation domains of CDA non-ribosomal peptide synthetase genes which provides evidence of gene shuffling between these domains. We also identify single nucleotide sequence inter-species differences which exist in the actinorhodin biosynthetic gene cluster. As the glyoxylate bypass is non-functional in both S. lividans strains due to the absence of the gene encoding isocitrate lyase it is likely that the ethylmalonyl-CoA pathway functions as the alternative mechanism for the assimilation of C2 compounds.ConclusionsThis study provides evidence for widespread genetic recombination, rather than it being focussed at 'hotspots', suggesting that the previously proposed 'archipelago model' of genomic differences between S. coelicolor and S. lividans is unduly simplistic. The two S. lividans strains investigated differ considerably in genetic complement, with TK24 lacking 175 more genes than its wild-type parent when compared to S. coelicolor. Additionally, we confirm the presence of bldB in S. lividans and deduce that S. lividans 66 and TK24, both deficient in the glyoxylate bypass, possess an alternative metabolic mechanism for the assimilation of C2 compounds. Given that streptomycetes generally display high genetic instability it is envisaged that these high-density arrays will find application for rapid assessment of genome content (particularly amplifications/deletions) in mutational studies of S. coelicolor and related species.

The Genome Sequence of Streptomyces lividans 66 Reveals a Novel tRNA-Dependent Peptide Biosynthetic System within a Metal-Related Genomic Island

“…Genomic hybridization experiments using an S. coelicolor M145 microarray and DNA from different S . lividans strains, showing the absence of several S. coelicolor genes from S. lividans , have also been reported (Jayapal et al 2007; Lewis et al 2010). Most of these genes are clustered within genomic islands, although it was also concluded that genetic variation among these strains might actually span throughout the entire chromosome (Lewis et al 2010).…”

“…lividans strains, showing the absence of several S. coelicolor genes from S. lividans , have also been reported (Jayapal et al 2007; Lewis et al 2010). Most of these genes are clustered within genomic islands, although it was also concluded that genetic variation among these strains might actually span throughout the entire chromosome (Lewis et al 2010). A good quality S. lividans genome sequence from a parental strain should provide further insights into the evolutionary processes leading to these intriguing genotypic and phenotypic differences.…”

Carboxylases in Natural and Synthetic Microbial Pathways

“…Recently, the ethylmalonyl-CoA pathway, which operates in ecologically relevant species, such as many alphaproteobacteria (Methylobacterium, Rhodobacter) and actinomycetes (Streptomyces), was discovered (41,44,79,92,110). In this acetylCoA assimilation strategy, two carboxylation reactions occur.…”

Response to Copper Stress in Streptomyces lividans Extends beyond Genes under Direct Control of a Copper-sensitive Operon Repressor Protein (CsoR)

“…S. coelicolor and Streptomyces lividans both display a distinct dependence on copper for development with that of S. lividans being more pronounced (18). They also share a high level of sequence identity and genome organization (19,20), and the gene numbering of the S. coelicolor genome database is used for S. lividans in this study. Sequence alignment of the S. lividans 4136 gene product with known CsoR orthologues reveals conservation of the amino acids that act as Cu(I)-binding ligands and two amino acids considered important for the Cu(I)-dependent allosteric regulation of DNA binding (Fig.…”