Unravelling the diversity of the cyclopiazonic acid family of mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS

Authors: UKA, VALDET - Ghent University; Moore, Geromy; ARROYO-MANZANARES, NATALIA - Ghent University; NEBIJA, DASHNOR - University Of Prishtina; DE SAEGER, SARAH - Ghent University; DIANA DI MAVUNGU, JOSE - Ghent University

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2017
Publication Date: 1/13/2017
Citation: Uka, V., Moore, G.G., Arroyo-Manzanares, N., Nebija, D., De Saeger, S., Diana Di Mavungu, J. 2017. Unravelling the diversity of the cyclopiazonic acid family of mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS. Toxins. 9:35. doi:10.3390/toxins9010035.

Interpretive Summary: Cyclopiazonic acid (CPA) is a neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures, approximately 40 years ago, its contribution to the A. flavus mycotoxin 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 in A. flavus cultures. In total, twenty-two CPA-type alkaloids were identified in extracts from the A. flavus strains examined. Thirteen of these metabolites have been previously reported in other fungi, but this is the first report of their existence in A. flavus. Two of our metabolite discoveries have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives in A. flavus cultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entire A. flavus mycotoxin problem.

Technical Abstract: Cyclopiazonic acid (a-cyclopiazonic acid, a-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures, approximately 40 years ago, its contribution to the A. flavus mycotoxin 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 in A. flavus cultures. 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 a-CPA fragmentation pattern. In total, twenty-two CPA-type alkaloids were identified in extracts from the A. flavus strains examined. Thirteen of these metabolites have been previously reported in other fungi, but this is the first report of their existence in A. flavus. Two of our metabolite discoveries have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives in A. flavus cultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entire A. flavus mycotoxin problem.