title: A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes.
abstract: BACKGROUND
  Recent advances in genome sequencing, combined with bioinformatic analysis, has led to the identification of numerous novel natural product gene clusters, particularly in actinomycetes of terrestrial and marine origin. Many of these gene clusters encode uncharacterised Type III polyketide synthases. To facilitate the study of these genes and their potentially novel products, we set out to construct an actinomycete expression host specifically designed for the heterologous expression of Type III PKS genes and their gene clusters.
  
  
  RESULTS
  A derivative of Streptomyces coelicolor A3(2) designed for the expression of Type III polyketide synthase (PKS) genes was constructed from the previously engineered expression strain S. coelicolor M1152 [Δact Δred Δcpk Δcda rpoB(C1298T)] by removal of all three of the endogenous Type III PKS genes (gcs, srsA, rppA) by PCR targeting. The resulting septuple deletion mutant, M1317, proved to be an effective surrogate host for the expression of actinobacterial Type III PKS genes: expression of the reintroduced gcs gene from S. coelicolor and of the heterologous rppA gene from Streptomyces venezuelae under the control of the constitutive ermE* promoter resulted in copious production of germicidin and flaviolin, respectively.
  
  
  CONCLUSIONS
  The newly constructed expression host S. coelicolor M1317 should be particularly useful for the discovery and analysis of new Type III polyketide metabolites.
authors.affiliation: Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. anyarat.thanapipatsiri@gmail.com.|Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK. anyarat.thanapipatsiri@gmail.com.
authors.forename: Anyarat
authors.initials: A
authors.lastname: Thanapipatsiri
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK. jan.claesen@ucsf.edu.|Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, CA, 94158, USA. jan.claesen@ucsf.edu.
authors.forename: Jan
authors.initials: J
authors.lastname: Claesen
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK. Juan-Pablo.Gomez-Escribano@jic.ac.uk.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Gomez-Escribano
authors.affiliation: Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK. mervyn.bibb@jic.ac.uk.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Bibb
authors.affiliation: Department of Genetics, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand. arinthip.t@ku.ac.th.|Center for Advanced Studies in Tropical Natural Resources, NRU-KU, Kasetsart University, Bangkok, 10900, Thailand. arinthip.t@ku.ac.th.
authors.forename: Arinthip
authors.initials: A
authors.lastname: Thamchaipenet
mesh_terms: D019149:Bioreactors; D005818:Genetic Engineering; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009285:Naphthoquinones / Q000378:metabolism; D030781:Organisms, Genetically Modified / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D011753:Pyrones / Q000378:metabolism; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism
chemical_list: D009285:Naphthoquinones; D011753:Pyrones; C082790:germicidin; C041659:flaviolin; D048630:Polyketide Synthases