title: Molecular and chemical characterization of the biosynthesis of the 6-MSA-derived meroterpenoid yanuthone D in Aspergillus niger.
abstract: Secondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA.
authors.affiliation: Eukaryotic Molecular Cell Biology Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 223, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Dorte K
authors.initials: DK
authors.lastname: Holm
authors.affiliation: Chemodiversity Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 221, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Lene M
authors.initials: LM
authors.lastname: Petersen
authors.affiliation: Metabolic Signaling and Regulation Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 221, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klitgaard
authors.affiliation: Fungal Physiology and Biotechnology Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 223, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Knudsen
authors.affiliation: Eukaryotic Molecular Cell Biology Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 223, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Zofia D
authors.initials: ZD
authors.lastname: Jarczynska
authors.affiliation: Metabolic Signaling and Regulation Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 221, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Kristian F
authors.initials: KF
authors.lastname: Nielsen
authors.affiliation: Department of Chemistry, Kemitorvet, Building 201, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Gotfredsen
authors.affiliation: Chemodiversity Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 221, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. Electronic address: tol@bio.dtu.dk.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Larsen
authors.affiliation: Eukaryotic Molecular Cell Biology Group, Department of Systems Biology, Center for Microbial Biotechnology, Soltofts Plads, Building 223, Technical University of Denmark, 2800 Kongens Lyngby, Denmark. Electronic address: um@bio.dtu.dk.
authors.forename: Uffe H
authors.initials: UH
authors.lastname: Mortensen
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001234:Aspergillus niger / Q000737:chemistry / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012459:Salicylates / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009097:Multienzyme Complexes; D012459:Salicylates; D054852:Small Molecule Libraries; D013729:Terpenes; C000595675:yanuthone D; D010088:Oxidoreductases; D000217:Acyltransferases; C021587:6-methylsalicylic acid synthetase; D008025:Ligases; C005236:6-methylsalicylic acid