<i>Aspergillus flavus</i> Secondary Metabolites: More than Just Aflatoxins

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.

Low aflatoxin levels and flowering delay inAspergillus flavus-resistant maize lines are correlated with increased corn earworm damage and enhanced seed fumonisin content

“…Given the highly variable distribution of AF in individual kernels of a maize ear (e.g., Lee et al 1980), it is possible that AF content particularly in damaged kernels (close to the silk canal, the site of inoculation as well as CEW infestation) was much greater than the average for the entire ear and high enough to be toxic to CEW survival. Furthermore, CEW may be sensitive also to other anti-insectan compounds made by A. flavus (Cary et al 2018) that could act additively or synergistically with AF (e.g., Kojic acid; Dowd 1988). Future experiments would involve late-maturing lines with A. flavus susceptibility and early maturing lines with A. flavus resistance to clarify and quantify the effects of flowering time and AF content on CEW infestation.…”

“…In spite of being a polyphagous pest with a remarkable capacity to metabolize a wide array of plant compounds, CEW has limited tolerance to AF and poor ability to metabolize the mycotoxin (Dowd 1988; Zeng et al 2006). The fungus is known to make several anti-insectan compounds, beside AF (TePaske et al 1992; Cary et al 2018). Other insect pests that are more tolerant may vector A. flavus (Zeng et al 2006; Opoku et al 2019).…”

Aflavinines: History, Biology and Total Synthesis

“…The studies on sclerotia of some species of Aspergillus genus was discussed by Soudo and co-workers [19]. Other various secondary metabolites of Aspergillus flavus are also discussed in the literature [20,21].…”

Chemical repertoire and biosynthetic machinery of the Aspergillus flavus secondary metabolome: A review

“…About 40 SMs have been chemically identified from culture of A. flavus; however, the link between many of these metabolites and their associated gene cluster is yet to be determined. The gene clusters with experimentally identified metabolites are the aflatoxin (Yu, Chang, et al, 2004), cyclopiazonic acid (CPA) (Seshime et al, 2009), aflatrem/aflavinines (Nicholson et al, 2009;Tang et al, 2015), ditryptophenaline (Saruwatari et al, 2014), piperazines (Forseth et al, 2013, kojic acid (Ammar, Srour, Ezzat, & Hoseny, 2017;Terabayashi et al, 2010), aspirochlorine (Chankhamjon et al, 2014), ustiloxin B (Umemura et al, 2014), asparasone (Cary et al, 2014), leporins (Cary, Uka, et al, 2015), bicoumarins (Cary, Han, et al, 2015), imizoquins (Khalid et al, 2017), aspergillic acid (Lebar et al, 2018), asperipin-2a Ye et al, 2019), and aspergillicin (Greco et al, 2019) biosynthesis gene clusters (Table 1). This implies that there remains a significant number of SM clusters and their associated metabolites to be identified and their biological functions determined.…”

“…Aspergillic acid biosynthesis. The gene cluster responsible for synthesis of these pyrazinones was recently identified and their biosynthetic pathway was determined (Lebar et al, 2018; Figure 9a). The backbone gene of the cluster (asaC) represents a noncanonical NRPS, composed of three catalytic domains, adenylation (A), peptidyl-carrier protein (PCP or thiolation [T] domain), and a short reductive (R) domain.…”