title: The complete genome sequence of the acarbose producer Actinoplanes sp. SE50/110.
abstract: BACKGROUND
  Actinoplanes sp. SE50/110 is known as the wild type producer of the alpha-glucosidase inhibitor acarbose, a potent drug used worldwide in the treatment of type-2 diabetes mellitus. As the incidence of diabetes is rapidly rising worldwide, an ever increasing demand for diabetes drugs, such as acarbose, needs to be anticipated. Consequently, derived Actinoplanes strains with increased acarbose yields are being used in large scale industrial batch fermentation since 1990 and were continuously optimized by conventional mutagenesis and screening experiments. This strategy reached its limits and is generally superseded by modern genetic engineering approaches. As a prerequisite for targeted genetic modifications, the complete genome sequence of the organism has to be known.
  
  
  RESULTS
  Here, we present the complete genome sequence of Actinoplanes sp. SE50/110 [GenBank:CP003170], the first publicly available genome of the genus Actinoplanes, comprising various producers of pharmaceutically and economically important secondary metabolites. The genome features a high mean G + C content of 71.32% and consists of one circular chromosome with a size of 9,239,851 bp hosting 8,270 predicted protein coding sequences. Phylogenetic analysis of the core genome revealed a rather distant relation to other sequenced species of the family Micromonosporaceae whereas Actinoplanes utahensis was found to be the closest species based on 16S rRNA gene sequence comparison. Besides the already published acarbose biosynthetic gene cluster sequence, several new non-ribosomal peptide synthetase-, polyketide synthase- and hybrid-clusters were identified on the Actinoplanes genome. Another key feature of the genome represents the discovery of a functional actinomycete integrative and conjugative element.
  
  
  CONCLUSIONS
  The complete genome sequence of Actinoplanes sp. SE50/110 marks an important step towards the rational genetic optimization of the acarbose production. In this regard, the identified actinomycete integrative and conjugative element could play a central role by providing the basis for the development of a genetic transformation system for Actinoplanes sp. SE50/110 and other Actinoplanes spp. Furthermore, the identified non-ribosomal peptide synthetase- and polyketide synthase-clusters potentially encode new antibiotics and/or other bioactive compounds, which might be of pharmacologic interest.
authors.affiliation: Senior research group in Genome Research of Industrial Microorganisms, Center for Biotechnology, Bielefeld University, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schwientek
authors.forename: Rafael
authors.initials: R
authors.lastname: Szczepanowski
authors.forename: Christian
authors.initials: C
authors.lastname: Rückert
authors.forename: Jörn
authors.initials: J
authors.lastname: Kalinowski
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein
authors.forename: Klaus
authors.initials: K
authors.lastname: Selber
authors.forename: Udo F
authors.initials: UF
authors.lastname: Wehmeier
authors.forename: Jens
authors.initials: J
authors.lastname: Stoye
authors.forename: Alfred
authors.initials: A
authors.lastname: Pühler
mesh_terms: D020909:Acarbose / Q000378:metabolism*; D000192:Actinomycetales / Q000235:genetics* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D002876:Chromosomes, Bacterial / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D019143:Evolution, Molecular; D018628:Gene Dosage / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D058977:Molecular Sequence Annotation; D005810:Multigene Family / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D020909:Acarbose