title: Characterization of the product of a nonribosomal peptide synthetase-like (NRPS-like) gene using the doxycycline dependent Tet-on system in Aspergillus terreus.
abstract: Genome sequencing of the fungus Aspergillus terreus uncovered a number of silent core structural biosynthetic genes encoding enzymes presumed to be involved in the production of cryptic secondary metabolites. There are five nonribosomal peptide synthetase (NRPS)-like genes with the predicted A-T-TE domain architecture within the A. terreus genome. Among the five genes, only the product of pgnA remains unknown. The Tet-on system is an inducible, tunable and metabolism-independent expression system originally developed for Aspergillus niger. Here we report the adoption of the Tet-on system as an effective gene activation tool in A. terreus. Application of this system in A. terreus allowed us to uncover the product of the cryptic NRPS-like gene, pgnA. Furthermore expression of pgnA in the heterologous Aspergillus nidulans host suggested that the pgnA gene alone is necessary for phenguignardic acid (1) biosynthesis.
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors: Wei-Wen
authors: WW
authors: Sun
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
authors: Chun-Jun
authors: CJ
authors: Guo
authors: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA; Department of Chemistry, University of Southern California, College of Letters, Arts, and Sciences, Los Angeles, CA 90089, USA. Electronic address: clayw@usc.edu.
authors: Clay C C
authors: CCC
authors: Wang
mesh_terms: D001230:Aspergillus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D001233:Aspergillus nidulans / Q000187:drug effects / Q000235:genetics; D001234:Aspergillus niger / Q000187:drug effects / Q000235:genetics; D001688:Biological Products / Q000378:metabolism; D004148:Dioxolanes / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology*; D005800:Genes, Fungal / Q000235:genetics*; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D001688:Biological Products; D004148:Dioxolanes; C575777:phenguignardic acid; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase; D004318:Doxycycline
keywords: Aspergillus terreus; Biosynthesis; Natural products; Nonribosomal peptide synthetase-like; Phenguignardic acid; Tet-on system