title: Unravelling the Diversity of the Cyclopiazonic Acid Family of Mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS.
abstract: Cyclopiazonic acid (α-cyclopiazonic acid, α-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminantAspergillus flavus. Despite its discovery inA. flavuscultures approximately 40 years ago, its contribution to theA. flavusmycotoxin burden is consistently minimized by our focus on the more potent carcinogenic aflatoxins also produced by this fungus. Here, we report the screening and identification of several CPA-type alkaloids not previously found inA. flavuscultures. Our identifications of these CPA-type alkaloids are based on a dereplication strategy involving accurate mass high resolution mass spectrometry data and a careful study of the α-CPA fragmentation pattern. In total, 22 CPA-type alkaloids were identified in extracts from theA. flavusstrains examined. Of these metabolites, 13 have been previously reported in other fungi, though this is the first report of their existence inA. flavus. Two of our metabolite discoveries, 11,12-dehydro α-CPA and 3-hydroxy-2-oxo CPA, have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives inA. flavuscultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entireA. flavusmycotoxin problem.
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. valdet.uka@ugent.be.|Department of Pharmacy, Faculty of Medicine, University of Prishtina, Rrethi i Spitalit p.n, 10000 Prishtina, Kosovo. valdet.uka@ugent.be.
authors.forename: Valdet
authors.initials: V
authors.lastname: Uka
authors.affiliation: Southern Regional Research Center, Agricultural Research Service, United States Department of Agriculture (ARS-USDA), New Orleans, 70124 LA, USA. geromy.moore@ars.usda.gov.
authors.forename: Geromy G
authors.initials: GG
authors.lastname: Moore
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. natalia.arroyomanzanares@ugent.be.|Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Campus Fuentenueva s/n, E-18071 Granada, Spain. natalia.arroyomanzanares@ugent.be.
authors.forename: Natalia
authors.initials: N
authors.lastname: Arroyo-Manzanares
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Prishtina, Rrethi i Spitalit p.n, 10000 Prishtina, Kosovo. dashnor.nebija@uni-pr.edu.
authors.forename: Dashnor
authors.initials: D
authors.lastname: Nebija
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. sarah.desaeger@ugent.be.
authors.forename: Sarah
authors.initials: S
authors.lastname: De Saeger
authors.affiliation: Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. jose.dianadimavungu@ugent.be.
authors.forename: José
authors.initials: J
authors.lastname: Diana Di Mavungu
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification*; D001231:Aspergillus flavus / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007211:Indoles / Q000302:isolation & purification*; D015394:Molecular Structure; D009183:Mycotoxins / Q000302:isolation & purification*; D009498:Neurotoxins / Q000302:isolation & purification*; D053719:Tandem Mass Spectrometry
chemical_list: D000470:Alkaloids; D007211:Indoles; D009183:Mycotoxins; D009498:Neurotoxins; C000543:cyclopiazonic acid
keywords: HRMS; cyclopiazonic acid; dereplication; ergot-like alkaloid