title: Multifactorial induction of an orphan PKS-NRPS gene cluster in Aspergillus terreus.
abstract: Mining the genome of the pathogenic fungus Aspergillus terreus revealed the presence of an orphan polyketide-nonribosomal-peptide synthetase (PKS-NRPS) gene cluster. Induced expression of the transcriptional activator gene adjacent to the PKS-NRPS gene was not sufficient for the activation of the silent pathway. Monitoring gene expression, metabolic profiling, and using a lacZ reporter strain allowed for the systematic investigation of physiological conditions that eventually led to the discovery of isoflavipucine and dihydroisoflavipucine. Phytotoxin formation is only activated in the presence of certain amino acids, stimulated at alkaline pH, but strictly repressed in the presence of glucose. Global carbon catabolite repression by CreA cannot be abolished by positive-acting factors such as PacC and overrides the pathway activator. Gene inactivation and stable isotope labeling experiments unveiled the molecular basis for flavipucine/fruit rot toxin biosynthesis.
authors.affiliation: Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology e.V., Hans Knoell Institute, Beutenbergstrasse 11a, Jena, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Gressler
authors.forename: Christoph
authors.initials: C
authors.lastname: Zaehle
authors.forename: Kirstin
authors.initials: K
authors.lastname: Scherlach
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
mesh_terms: D001119:Arginase / Q000235:genetics; D001230:Aspergillus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002241:Carbohydrates / Q000494:pharmacology; D057465:Catabolite Repression / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D056426:Genetic Loci / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D007763:Lac Operon / Q000235:genetics; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009183:Mycotoxins / Q000096:biosynthesis; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011728:Pyridones / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D002241:Carbohydrates; D009183:Mycotoxins; D011728:Pyridones; C002860:flavipucine; D048630:Polyketide Synthases; D001119:Arginase; D007930:Leucine