The erythromycin biosynthetic gene cluster of Aeromicrobium erythreum

The erythromycin-biosynthetic (ery) gene cluster of Aeromicrobium erythreum was cloned and characterized. The 55.4-kb cluster contains 25 ery genes. Homologues were found for each gene in the previously characterized ery gene cluster from Saccharopolyspora erythraea. In addition, four new predicted ery genes were identified. Two of the new predicted genes, coding for a phosphopantetheinyl transferase (eryP) and a type II thioesterase (eryTII), were internal to the ery cluster. The other two new genes, coding for a thymidine 5'-diphosphate-glucose synthase (eryDI) and a MarR-family transcriptional repressor (ery-ORF25), were found at the two ends of the ery cluster. A knockout in eryDI showed it to be essential for erythromycin biosynthesis. The gene order of the two ery clusters was conserved within a core region of 15 contiguous genes, with the exception of IS1136 which was not found in the A. erythreum cluster. Beyond the core region, gene shuffling had occurred between the two sides of the cluster. The flanking regions of the two ery clusters were not alike in the type of genes found.