title: Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus calidoustus.
abstract: Filamentous fungi produce a wide range of natural products that are commonly used in various industrial contexts (e.g., pharmaceuticals and insecticides). Meroterpenoids are natural products of interest because of their various biological activities. Among the meroterpenoids, there is a group of insecticidal compounds known as the austinoids. These compounds have also been studied because of their intriguing spiro-lactone ring formation along with various modifications. Here, we present an extension of the original austinol/dehydroaustinol biosynthesis pathway from Aspergillus nidulans in the recently identified filamentous fungus Aspergillus calidoustus. Besides the discovery and elucidation of further derivatives, genome mining led to the discovery of new putative biosynthetic genes. The genes involved in the biosynthesis of later austinoid products were characterized, and among them was a second polyketide synthase gene in the A. calidoustus cluster that was unusual because it was a noninterative polyketide synthase producing a diketide. This diketide product was then loaded onto the austinoid backbone, resulting in a new insecticidal derivative, calidodehydroaustin.
authors.forename: Vito
authors.identifier: 0000-0002-4405-169X
authors.initials: V
authors.lastname: Valiante
authors.affiliation: Friedrich Schiller University , 07745 Jena, Germany.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Mattern
authors.affiliation: Institute of Biotechnology and Drug Research , Erwin-Schroedinger-Strasse 56, 67663 Kaiserslautern, Germany.|Johannes-Gutenberg-University Mainz , Institute of Biotechnology, Johann-Joachim-Becherweg 15, 55128 Mainz, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schüffler
authors.forename: Fabian
authors.identifier: 0000-0002-4070-3400
authors.initials: F
authors.lastname: Horn
authors.forename: Grit
authors.initials: G
authors.lastname: Walther
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.affiliation: BASF SE , 67056 Ludwigshafen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Petzke
authors.affiliation: BASF SE , 67056 Ludwigshafen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Dickhaut
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: Friedrich Schiller University , 07745 Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.forename: Markus
authors.initials: M
authors.lastname: Nett
authors.affiliation: Institute of Biotechnology and Drug Research , Erwin-Schroedinger-Strasse 56, 67663 Kaiserslautern, Germany.|Johannes-Gutenberg-University Mainz , Institute of Biotechnology, Johann-Joachim-Becherweg 15, 55128 Mainz, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thines
authors.affiliation: Friedrich Schiller University , 07745 Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D001230:Aspergillus / Q000201:enzymology / Q000378:metabolism*; D001233:Aspergillus nidulans / Q000201:enzymology / Q000378:metabolism; D053898:Biosynthetic Pathways; D019281:Dimerization; D005800:Genes, Fungal; D007306:Insecticides; D053858:Metabolic Networks and Pathways; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides / Q000378:metabolism; D013729:Terpenes / Q000378:metabolism*
chemical_list: D007306:Insecticides; D061065:Polyketides; D013729:Terpenes; C573071:austinol; D048630:Polyketide Synthases