Aspergillus flavus secondary metabolites: more than just aflatoxins

Authors: Cary, Jeffrey; Gilbert, Matthew; Lebar, Matthew; Majumdar, Raj; CALVO, ANA - Northern Illinois University

Submitted to: Food Safety
Publication Type: Review Article
Publication Acceptance Date: 3/8/2018
Publication Date: 3/30/2018
Citation: Cary, J.W., Gilbert, M.K., Lebar, M.D., Majumdar, R., Calvo, A.M. 2018. Aspergillus flavus secondary metabolites: more than just aflatoxins. Food Safety. 6(1):7-32. https://doi.org/10.14252/foodsafetyfscj.2017024.
DOI: https://doi.org/10.14252/foodsafetyfscj.2017024

Interpretive Summary: The fungus, Aspergillus flavus, is best known for producing the family of potent carcinogenic compounds known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other compounds called secondary metabolites, many of which have also been shown to be toxic. It has been shown that the genes responsible for production of secondary metabolites in A. flavus and other fungi are grouped into distinct clusters of genes on the chromosomes. While about forty secondary metabolites have been identified from A. flavus, sequencing of the fungus’ DNA indicates that there are additional gene clusters predicted to be capable of producing even more of these compounds. Many of these secondary metabolite gene clusters are not active during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene clusters to allow identification of the associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal growth, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.

Technical Abstract: Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of these secondary metabolites have been identified from A. flavus cultures, analysis of the genome has predicted the existence of at least 56 secondary metabolite gene clusters. Many of these gene clusters are not expressed during growth of the fungus on standard laboratory media. This presents researchers with a major challenge of devising novel strategies to manipulate the fungus and its genome so as to activate secondary metabolite gene expression and allow identification of associated cluster metabolites. In this review, we discuss the genetic, biochemical and bioinformatic methods that are being used to identify previously uncharacterized secondary metabolite gene clusters and their associated metabolites. It is important to identify as many of these compounds as possible to determine their bioactivity with respect to fungal development, survival, virulence and especially with respect to any potential synergistic toxic effects with aflatoxin.