title: A highly unusual polyketide synthase directs dawenol polyene biosynthesis in Stigmatella aurantiaca.
abstract: Enormous progress in the field of polyketide biosynthesis has led to the establishment of rules for general text book biosynthetic logic and consequently to the assumption that biosynthetic genes can be easily correlated with the corresponding natural products. However, non-textbook examples of polyketide assembly continue to be discovered suggesting the gene to product and product to gene predictions need improvement, especially as they are increasingly used in the post-genomic era. Here, we analyzed the genomic blueprint of a myxobacterial multi-producer of secondary metabolites, Stigmatella aurantiaca DW4/3-1, for its biosynthetic potential by genome-mining. In addition to the five polyketide synthase and/or nonribosomal peptide synthetase gene clusters of known function we identified a further 13 genomic regions exemplifying the enormous genetic potential for the production of additional chemical diversity by this strain. We show by gene inactivation and heterologous expression of the newly identified biosynthetic pathway for dawenol that the biosynthesis of this known polyene does not follow text book biosynthetic logic. Intriguingly, a genomic locus encoding an unusual polyketide synthase exhibiting similarity to gene loci involved in the formation of polyunsaturated fatty acids and secondary lipids was identified.
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: Corina
authors.initials: C
authors.lastname: Oßwald
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: Nestor
authors.initials: N
authors.lastname: Zaburannyi
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: Christian
authors.initials: C
authors.lastname: Burgard
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: Thomas
authors.initials: T
authors.lastname: Hoffmann
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: s.wenzel@mx.uni-saarland.de.
authors.forename: Silke C
authors.initials: SC
authors.lastname: Wenzel
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; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, University Campus Building C2.3, 66123 Saarbrücken, Germany. Electronic address: rom@helmholtz-hzi.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D053898:Biosynthetic Pathways; D009097:Multienzyme Complexes / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics; D011090:Polyenes / Q000737:chemistry / Q000378:metabolism*; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D020606:Stigmatella aurantiaca / Q000201:enzymology*
chemical_list: D009097:Multienzyme Complexes; D011090:Polyenes; D048630:Polyketide Synthases; D010453:Peptide Synthases
keywords: Dawenol; Genome-mining; Iterative polyketide synthase; PUFA-like polyketide synthase; Secondary lipid synthase