Oxidative Stress-Related Transcription Factors in the Regulation of Secondary Metabolism

Abstract

There is extensive and unequivocal evidence that secondary metabolism in filamentous fungi and plants is associated with oxidative stress. In support of this idea, transcription factors related to oxidative stress response in yeast, plants, and fungi have been shown to participate in controlling secondary metabolism. Aflatoxin biosynthesis, one model of secondary metabolism, has been demonstrated to be triggered and intensified by reactive oxygen species buildup. An oxidative stress-related bZIP transcription factor AtfB is a key player in coordinate expression of antioxidant genes and genes involved in aflatoxin biosynthesis. Recent findings from our laboratory provide strong support for a regulatory network comprised of at least four transcription factors that bind in a highly coordinated and timely manner to promoters of the target genes and regulate their expression. In this review, we will focus on transcription factors involved in co-regulation of aflatoxin biosynthesis with oxidative stress response in aspergilli, and we will discuss the relationship of known oxidative stress-associated transcription factors and secondary metabolism in other organisms. We will also talk about transcription factors that are involved in oxidative stress response, but have not yet been demonstrated to be affiliated with secondary metabolism. The data support the notion that secondary metabolism provides a secondary line of defense in cellular response to oxidative stress.

Redox Metabolites Signal Polymicrobial Biofilm Development via the NapA Oxidative Stress Cascade in Aspergillus

“…While the redox activity of 1-Me-PHZ can modulate Aspergillus development, PCA and 1-OH-PHZ have been reported to differentially affect Aspergillus siderophore production [16], suggesting that metabolite conversions by neighboring microbes can affect mixed-species biofilms in multiple ways. Pertinent to these findings, fungal secondary metabolism (including siderophore production) and oxidative stress response have been recently implied to be co-regulated in a highly coordinated manner by NapA and another bZIP protein, AtfB [27, 49]. Going forward, it will be of interest to explore whether phenazines (and other redox metabolites) can also direct Aspergillus secondary metabolism via the active oxidative stress response.…”

A transcription factor, MrMsn2, in the dimorphic fungus Metarhizium rileyi is essential for dimorphism transition, aggravated pigmentation, conidiation and microsclerotia formation

“…Secondary metabolism, such as pigments production, is triggered and intensified by ROS build‐up, with pigments being important for protecting the fungi against stress conditions (Cho et al ., 2012; Hong et al ., 2013). In the absence of MrMsn2 aggravated pigmentation and pigment synthesis‐associated genes were significantly upregulated during conidiation in ▵MrMsn2 mutants.…”

“…As the core of signalling pathway, fungal TFs are important for transcriptional regulation of gene expression during cellular growth, secondary metabolism, stress responses and pathogenesis (Klug, 2010; Hong et al ., 2013; Liu et al ., 2013; Marinho et al ., 2014; Zhang et al ., 2014; Huang et al ., 2015; Shelest, 2017; Yin et al ., 2017; Song et al ., 2018). …”

Aflatoxins: biosynthesis, prevention and eradication

“…Disruption in the AF biosynthetic pathway at an early, middle, or late steps, affected quantities of detected ROS (Roze et al, 2015). AF production apparently could direct the ROS excess accumulated during cell ageing, or as a response to external insults, into extending the fungal lifespan (Hong et al, 2013). AFB 1 biosynthesis is controlled by a wider array of oxidative stress factors, such as lipid hydroperoxide, superoxide, and hydroxyl and thiol radicals (Grintzalis et al, 2014).…”