title: Evaluation of the Synthetic Potential of an AHBA Knockout Mutant of the Rifamycin Producer Amycolatopsis mediterranei.
abstract: Supplementing an AHBA(-) mutant strain of Amycolatopsis mediterranei, the rifamycin producer, with a series of benzoic acid derivatives yielded new tetraketides containing different phenyl groups. These mutasynthetic studies revealed unique reductive properties of A. mediterranei towards nitro- and azidoarenes, leading to the corresponding anilines. In selected cases, the yields of mutaproducts (fermentation products isolated after feeding bacteria with chemically prepared analogs of natural building blocks) obtained are in a range (up to 118 mg L(-1)) that renders them useful as chiral building blocks for further synthetic endeavors. The configuration of the stereogenic centers at C6 and C7 was determined to be 6R,7S for one representative tetraketide. Importantly, processing beyond the tetraketide stage is not always blocked when the formation of the bicyclic naphthalene precursor cannot occur. This was proven by formation of a bromo undecaketide, an observation that has implications regarding the evolutionary development of rifamycin biosynthesis.
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany).
authors.forename: Ilona
authors.initials: I
authors.lastname: Bułyszko
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany).
authors.forename: Gerald
authors.initials: G
authors.lastname: Dräger
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany).
authors.forename: Anja
authors.initials: A
authors.lastname: Klenge
authors.affiliation: Institute of Organic Chemistry and Center of Biomolecular Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany). andreas.kirschning@oci.uni-hannover.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirschning
mesh_terms: D000192:Actinomycetales / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001386:Azides / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006836:Hydro-Lyases / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000737:chemistry*; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D048630:Polyketide Synthases / Q000737:chemistry* / Q000378:metabolism; D012294:Rifamycins / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001386:Azides; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D009097:Multienzyme Complexes; D009281:Naphthalenes; D012294:Rifamycins; D048630:Polyketide Synthases; C111160:3-amino-5-hydroxybenzoic acid synthase; D006836:Hydro-Lyases
keywords: antibiotics; azides; mutasynthesis; natural products; polyketide synthase