title: Completing the puzzle of aurachin biosynthesis in Stigmatella aurantiaca Sg a15.
abstract: The aurachins are a family of secondary metabolites, with the main members aurachin A, B, C, and D, produced by the myxobacterium Stigmatella aurantiaca Sg a15. These isoprenoid quinoline alkaloids are classified as A-type or C-type aurachins according to the position of the farnesyl residue either at C4 or C3 of the quinoline core, respectively. Previous feeding studies revealed that the C-type aurachins are converted to A-type aurachins by late stage tailoring reactions. While the core gene cluster coding for the functionalities required for the biosynthesis of the basic structure aurachin D is known, neither of the genes encoding for the successively acting tailoring enzymes was known up to date, which was assumed to be due to a split cluster organisation. Here we describe the identification of a total of five genes, located upstream of the aurachin core cluster and at additional two loci elsewhere in the genome, encoding for the aforementioned functionalities. The generation and evaluation of respective inactivation mutants of S. aurantiaca Sg a15 allowed for the first time to propose an exhaustive model for aurachin biosynthesis. One of the deduced biosynthetic transformations corresponds to a pinacol rearrangement, an unprecedented tailoring reaction in secondary metabolite biosynthesis.
authors: Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research, Helmholtz Center for Infection Research, Saarland University, PO Box 151150, 66041 Saarbrücken, Germany.
authors: Dominik
authors: D
authors: Pistorius
authors: Yanyan
authors: Y
authors: Li
authors: Axel
authors: A
authors: Sandmann
authors: Rolf
authors: R
authors: Müller
mesh_terms: D001483:Base Sequence; D053898:Biosynthetic Pathways; D003500:Cyclization; D005798:Genes, Bacterial; D006900:Hydroxylation; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism; D015363:Quinolones / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020606:Stigmatella aurantiaca / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D011804:Quinolines; D015363:Quinolones; C052095:aurachin B; C052097:aurachin D; C052096:aurachin C; C052094:aurachin A; D006899:Mixed Function Oxygenases; D010105:Oxygenases