title: Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin.
abstract: To reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, we created a "genetic dereplication" strain in which we deleted eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total). This strain allowed us to discover a novel compound that we designate aspercryptin and to propose a biosynthetic pathway for the compound. Interestingly, aspercryptin is formed from compounds produced by two separate gene clusters, one of which makes the well-known product cichorine. This raises the exciting possibility that fungi use differential regulation of expression of secondary metabolite gene clusters to increase the diversity of metabolites they produce.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA.|Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, 71710, Taiwan.
authors.forename: Yi-Ming
authors.identifier: http://orcid.org/0000-0001-9899-1364
authors.initials: YM
authors.lastname: Chiang
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA.|Industrial Biotechnology Division, Reliance Technology Group, Reliance Industries Limited, Reliance Corporate Park, Thane Belapur Road, Ghansoli, Navi, Mumbai, 400701, India.
authors.forename: Manmeet
authors.initials: M
authors.lastname: Ahuja
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA.
authors.forename: C Elizabeth
authors.initials: CE
authors.lastname: Oakley
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Entwistle
authors.affiliation: Del Shankel Structural Biology Center, University of Kansas, Lawrence, KS, 66045, USA.
authors.forename: Anabanadam
authors.initials: A
authors.lastname: Asokan
authors.affiliation: Institute for Milk Hygiene, University of Veterinary Medicine Vienna, Vienna, 1210, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zutz
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA.|Department of Chemistry, University of Southern California, Los Angeles, CA, 90089, USA.
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA. boakley@ku.edu.
authors.forename: Berl R
authors.identifier: http://orcid.org/0000-0002-3046-8240
authors.initials: BR
authors.lastname: Oakley
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D005800:Genes, Fungal; D009842:Oligopeptides / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; C000611661:aspercryptin
keywords: NRPS; aspergillus; biosynthesis; genetic dereplication; natural products