GAC1, a gene encoding a putative GTPase-activating protein, regulates bikaverin biosynthesis inFusarium verticillioides

Abstract

Fusarium verticillioides (teleomorph Gibberella moniliformis) is an ascomycete known to produce a variety of secondary metabolites, including fumonisins, fusaric acid and bikaverin. These metabolites are synthesized when the fungus is under stress, notably nutrient limitations. To date we have limited understanding of the complex regulatory process associated with fungal secondary metabolism. In this study we generated a collection of F. verticillioides mutants by using REMI (restriction enzyme mediated integration) mutagenesis and in the process identified a strain, R647, that carries a mutation in a gene designated GAC1. Mutation in the GACI locus, which encodes a putative GTPase activating protein, resulted in the increased production of bikaverin, suggesting that GAC1 is negatively associated with bikaverin biosynthesis. Complementation of R647 with the wildtype GAC1 gene restored the bikaverin production level to that of the wild-type progenitor, demonstrating that gac1 mutation was directly responsible for the overproduction of bikaverin. We also demonstrated that AREA, encoding global nitrogen regulator, and PKS4, encoding polyketide synthase, are downstream genes that respectively are regulated positively and negatively by GAC1. Our results suggest that GAC1 plays an important role in signal transduction regulating bikaverin production in F. verticillioides.

Adenylyl cyclase regulates heavy metal sensitivity, bikaverin production and plant tissue colonization in Fusarium proliferatum

“…Here were presented proofs, that not only GAC1, but Fpacy1, a downstream element of the cAMP-PKA signaling pathway also represses the biosynthesis of this secondary metabolite. On the other hand, mutations of neither the GAC1 gene of F. verticillioides [43], nor Fpacy1 of F. proliferatum (present study) affected FB1 biosynthesis. The stress stimuli needed to trigger fumonisin biosynthesis is mediated via another signaling pathway, the HOG-type MAPK route, as has recently been demonstrated [44].…”

“…Bikaverin is a polyketide secondary metabolite with antiprotozoal and antifungal activity [18,41] and its production is triggered by stress factors, like nitrogen depletion [42]. Recent studies demonstrated that GAC1, a putative GTPase activator protein gene of Fusarium verticillioides (a close relative of F. proliferatum) negatively regulates bikaverin production [43]. The authors postulated that GAC1 is involved in trafficking proteins through the nucleus membrane and they necessitated further research to understand the signaling pathway that directly regulates bikaverin synthesis.…”

Caripyrin, a new inhibitor of infection-related morphogenesis in the rice blast fungus Magnaporthe oryzae

“…20 Fusaric acid (2) has been described to be produced in Fusarium verticillioides under stress conditions, notably, nutrient limitations. 21 The metabolite has been described as an inhibitor of metal-containing oxidative enzymes, such as dopamine-b-hydroxylases, phenylethanolamine methyltransferase and catechol oxidase. 22 Nonpathogenic Fusarium oxysporum species have been described as an potential biocontrol agents, producing only 2 and dehydrofusaric acid, but no other toxins.…”

Effects of temperature and incubation time on growth and ochratoxin A biosynthesis by Aspergillus carbonarius and Aspergillus ochraceus in grain-based media

“…OTA biosynthesis may be influenced by eco physiological intrinsic factors, such as temperature, nitrogen shortage and pH conditions which also influence germination, growth and sporulation (Palacios-Cabrera et al, 2005;Garcia-Cela et al, 2014;Passamani et al, 2014). Under stress conditions, the signaling pathways certainly induce the production of mycotoxins (Choi et al, 2008;Kohut et al, 2009).Therefore, understanding the effects of these factors can help reduce mycotoxins, both in the field and during storage. Furthermore, interactions between mycotoxigenic species and other spoilage fungi can significantly influence ochratoxin A production (Lee and Magan, 2000).Several authors have studied the ability of A. ochraceus and A. carbonarius to produce OTA in coffee, maize and synthetic grape and barley medium under different environmental conditions (Pardo et al, 2005;Lee and Magan, 2000;Marín et al, 2006;Pardo et al, 2004;Garcia et al, 2011).…”