The sequence of a 1.8-Mb bacterial linear plasmid reveals a rich evolutionary reservoir of secondary metabolic pathways

Marnix H. Medema, Axel Trefzer, Andriy Kovalchuk, Marco Van Den Berg, Ulrike Müller, Wilbert Heijne, Liang Wu, Mohammad T. Alam, Catherine M. Ronning, William C. Nierman, Roel A.L. Bovenberg, Rainer Breitling, Eriko Takano

Research output: Contribution to journalArticlepeer-review

161 Citations (Scopus)

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 ofadiverse arrayofbiotechnologically important secondary metabolites, revealedagiantlinear plasmidof1.8 Mb in length. This megaplasmid (pSCL4)isone ofthe largest plasmids ever identified and the largest linear plasmidto 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 plasmidis densely packed with anexceptionally large numberofgene clusters for the potential production of secondary metabolites, including a large number of putative antibiotics, such as staurosporine, moenomycin, β-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.

Original languageEnglish
Pages (from-to)212-224
Number of pages13
JournalGenome Biology and Evolution
Volume2
Issue number1
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • Chromosomal evolution
  • Genome sequence
  • Natural products
  • Streptomyces clavuligerus

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

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