title: Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A.
abstract: Aspergillus aculeatus, a filamentous fungus belonging to the Aspergillus clade Nigri, is an industrial workhorse in enzyme production. Recently we reported a number of secondary metabolites from this fungus; however, its genetic potential for the production of secondary metabolites is vast. In this study we identified a 6-methylsalicylic acid (6-MSA) synthase from A. aculeatus, and verified its functionality by episomal expression in A. aculeatus and heterologous expression in A. nidulans. Feeding studies with fully (13) C-labeled 6-MSA revealed that 6-MSA is incorporated into aculinic acid, which further incorporates into three compounds that we name aculins A and B, and epi-aculin A, described here for the first time. Based on NMR data and bioinformatic studies we propose the structures of the compounds as well as a biosynthetic pathway leading to formation of aculins from 6-MSA.
authors.affiliation: Natural Product Discovery, Eukaryotic Biotechnology, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 221, 2800, Kgs. Lyngby, Denmark.
authors.forename: Lene M
authors.initials: LM
authors.lastname: Petersen
authors.affiliation: Eukaryotic Molecular Cell Biology Group, Eukaryotic Biotechnology, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 223, 2800, Kgs. Lyngby, Denmark.
authors.forename: Dorte K
authors.initials: DK
authors.lastname: Holm
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, 2800, Kgs. Lyngby, Denmark.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Gotfredsen
authors.affiliation: Eukaryotic Molecular Cell Biology Group, Eukaryotic Biotechnology, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 223, 2800, Kgs. Lyngby, Denmark. um@bio.dtu.dk.
authors.forename: Uffe H
authors.initials: UH
authors.lastname: Mortensen
authors.affiliation: Natural Product Discovery, Eukaryotic Biotechnology, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 221, 2800, Kgs. Lyngby, Denmark. tol@bio.dtu.dk.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Larsen
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000378:metabolism*; D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D001230:Aspergillus / Q000201:enzymology* / Q000235:genetics*; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism*; D012459:Salicylates / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000085:Acetates; D009097:Multienzyme Complexes; D011753:Pyrones; D012459:Salicylates; D011392:Proline; D010088:Oxidoreductases; D000217:Acyltransferases; C021587:6-methylsalicylic acid synthetase; D008025:Ligases; C005236:6-methylsalicylic acid
keywords: Aspergillus; biosynthesis; methylsalicylic acid; natural products; polyketide; terpene