title: Heterologous expression of an orphan NRPS gene cluster from Paenibacillus larvae in Escherichia coli revealed production of sevadicin.
abstract: The Gram-positive bacterium Paenibacillus larvae is the causative agent of the fateful honey bee disease American Foulbrood (AFB). Sequence analysis of P. larvae genomic DNA showed the presence of numerous nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) encoding gene clusters, not correlating with secondary metabolite production. As NRPS and PKS derived metabolites are known to exhibit diverse biological activities, their identification is of particular interest for infection and drug research. Here an 11.6kb orphan NRPS gene cluster was directly cloned from the genomic DNA of P. larvae and expressed in Escherichia coli resulting in the production of sevadicin. Isolation of the metabolite was followed by structural characterization, synthesis and bioactivity studies.
authors.affiliation: Hunan Provincial Key Laboratory for Microbial Molecular Biology-State Key Laboratory Breeding Base of Microbial Molecular Biology, College of Life Science, Hunan Normal University, 410081 Changsha, PR China; Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research & Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research & Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Frewert
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research & Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harmrolfs
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research & Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: Institute for Organic Chemistry, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Karmann
authors.affiliation: Institute for Organic Chemistry, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Uli
authors.initials: U
authors.lastname: Kazmaier
authors.affiliation: Hunan Provincial Key Laboratory for Microbial Molecular Biology-State Key Laboratory Breeding Base of Microbial Molecular Biology, College of Life Science, Hunan Normal University, 410081 Changsha, PR China.
authors.forename: Liqiu
authors.initials: L
authors.lastname: Xia
authors.affiliation: Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Life Science College, Shandong University, 250100 Jinan, PR China. Electronic address: zhangyouming@sdu.edu.cn.
authors.forename: Youming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbial Natural Products, Helmholtz-Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research & Pharmaceutical Biotechnology, Saarland University, 66123 Saarbrücken, Germany. Electronic address: rom@helmholtz-hzi.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D056507:Paenibacillus / Q000201:enzymology* / Q000235:genetics*; D010453:Peptide Synthases / Q000235:genetics*; D048630:Polyketide Synthases / Q000235:genetics*
chemical_list: D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase
keywords: American Foulbrood; Direct cloning; Heterologous expression; Paenibacillus larvae; Sevadicin