title: The sequence of a 1.8-mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways.
abstract: Plasmids are mobile genetic elements that play a key role in the evolution of bacteria by mediating genome plasticity and lateral transfer of useful genetic information. Although originally considered to be exclusively circular, linear plasmids have also been identified in certain bacterial phyla, notably the actinomycetes. In some cases, linear plasmids engage with chromosomes in an intricate evolutionary interplay, facilitating the emergence of new genome configurations by transfer and recombination or plasmid integration. Genome sequencing of Streptomyces clavuligerus ATCC 27064, a Gram-positive soil bacterium known for its production of a diverse array of biotechnologically important secondary metabolites, revealed a giant linear plasmid of 1.8 Mb in length. This megaplasmid (pSCL4) is one of the largest plasmids ever identified and the largest linear plasmid to be sequenced. It contains more than 20% of the putative protein-coding genes of the species, but none of these is predicted to be essential for primary metabolism. Instead, the plasmid is densely packed with an exceptionally large number of gene clusters for the potential production of secondary metabolites, including a large number of putative antibiotics, such as staurosporine, moenomycin, beta-lactams, and enediynes. Interestingly, cross-regulation occurs between chromosomal and plasmid-encoded genes. Several factors suggest that the megaplasmid came into existence through recombination of a smaller plasmid with the arms of the main chromosome. Phylogenetic analysis indicates that heavy traffic of genetic information between Streptomyces plasmids and chromosomes may facilitate the rapid evolution of secondary metabolite repertoires in these bacteria.
authors.affiliation: Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
authors.forename: Marnix H
authors.initials: MH
authors.lastname: Medema
authors.forename: Axel
authors.initials: A
authors.lastname: Trefzer
authors.forename: Andriy
authors.initials: A
authors.lastname: Kovalchuk
authors.forename: Marco
authors.initials: M
authors.lastname: van den Berg
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
authors.forename: Wilbert
authors.initials: W
authors.lastname: Heijne
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Alam
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Ronning
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Roel A L
authors.initials: RA
authors.lastname: Bovenberg
authors.forename: Rainer
authors.initials: R
authors.lastname: Breitling
authors.forename: Eriko
authors.initials: E
authors.lastname: Takano
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D010957:Plasmids / Q000235:genetics*; D012093:Replicon; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial