RmtA, a Putative Arginine Methyltransferase, Regulates Secondary Metabolism and Development in Aspergillus flavus

Abstract

Aspergillus flavus colonizes numerous oil seed crops such as corn, peanuts, treenuts and cotton worldwide, contaminating them with aflatoxin and other harmful potent toxins. In the phylogenetically related model fungus Aspergillus nidulans, the methyltransferase, RmtA, has been described to be involved in epigenetics regulation through histone modification. Epigenetics regulation affects a variety of cellular processes, including morphogenesis and secondary metabolism. Our study shows that deletion of rmtA in A. flavus results in hyperconidiating colonies, indicating that rmtA is a repressor of asexual development in this fungus. The increase in conidiation in the absence of rmtA coincides with greater expression of brlA, abaA, and wetA compared to that in the wild type. Additionally, the rmtA deletion mutant presents a drastic reduction or loss of sclerotial production, while forced expression of this gene increased the ability of this fungus to generate these resistant structures, revealing rmtA as a positive regulator of sclerotial formation. Importantly, rmtA is also required for the production of aflatoxin B1 in A. flavus, affecting the expression of aflJ. Furthermore, biosynthesis of additional metabolites is also controlled by rmtA, indicating a broad regulatory output in the control of secondary metabolism. This study also revealed that rmtA positively regulates the expression of the global regulatory gene veA, which could contribute to mediate the effects of rmtA on development and secondary metabolism in this relevant opportunistic plant pathogen.

Aspergillus nidulans in the post-genomic era: a top-model filamentous fungus for the study of signaling and homeostasis mechanisms

“…This is, for example, a way to induce the sterigmatocystin (stc) gene cluster (mycotoxin production) and the wA gene cluster (spore pigmentation) (Kurtz and Champe 1982;Brown et al 1996;Inglis et al 2013). Directly related to this approach is the use of mutant backgrounds in which development or other key cellular processes are delayed or halted, as for example the absence of FlbB, FlbD, or AslA (transcriptional regulators of conidiation; see before); CsnE (COP9 signalosome component), MtfA, and McrA (zinc finger-type transcription factors); or the chromatin remodelers KdmB, RmtA, and EsaA (Soukup et al 2012;Ramamoorthy et al 2013;Gerke and Braus 2014;Oiartzabal-Arano et al 2015;Gacek-Matthews et al 2016;Oakley et al 2016;Satterlee et al 2016;Kim et al 2017). More sophisticated approaches have deleted/ overexpressed specific genes within a cluster, heterologously expressed secondary metabolite genes in A. nidulans or swapped domains within specific PKSs (see, for example, Chiang et al 2013;Yeh et al 2013).…”

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

“…Examples include RmtA, a putative arginine methyltransferase, shown to be required for production of normal levels of AFB 1 and other uncharacterized SMs 97) . Similar regulation of SM production in A. flavus was also observed by RtfA, a putative RNAPol II transcription elongation factor, in coordination with VeA and LaeA 98) .…”

Advances in molecular and genomic research to safeguard food and feed supply from aflatoxin contamination

“…A ΔrtfA mutant exhibited a significant decrease in sclerotial and aflatoxin production as well as other uncharacterised SMs. Another epigenetic factor controlling development and aflatoxin production in A. flavus is the histone-modifying methyltransferase, RmtA (Satterlee et al, 2016). RmtA was shown to be a positive regulator of sclerotial production while suppressing conidiation and aflatoxin production.…”