Genome scale metabolic model combined with single molecule real-time sequencing to analyze Actinomycete chromosomal heterogeneity.

The rapid development of biotechnology has provided new perspectives to observe and helped to gradually understand the significance of genetic instability in Actinobacteria. High frequency deletions of extremities and abnormal methylation of chromosomes suggest there might be relevant between the two phenomena. With this suspicion, we used single molecule real-time (SMRT) sequencing to map the genome-level methylation of one branch of actinomycetes, Saccharopolyspora erythraea, which have ring-shaped chromosomes. S. erythraea used for analysis in this study shares the same highly unstable phenotypic traits, as evidenced by diverse spore morphology and fluctuating erythromycin production. Multiple amplification of genomic islands closes to the replication initiation site and 6-methyladenine (m6A) deletion in genomic islands suggest that the interaction between the restriction modification (R-M) system and transposable elements provides an explanation for the division of labor by genomic heterogeneity in actinomycetes.