Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Nov 28:5:656.
doi: 10.3389/fmicb.2014.00656. eCollection 2014.

Nitrogen regulation of fungal secondary metabolism in fungi

Affiliations
Review

Nitrogen regulation of fungal secondary metabolism in fungi

Bettina Tudzynski. Front Microbiol. .

Abstract

Fungi occupy diverse environments where they are constantly challenged by stressors such as extreme pH, temperature, UV exposure, and nutrient deprivation. Nitrogen is an essential requirement for growth, and the ability to metabolize a wide variety of nitrogen sources enables fungi to colonize different environmental niches and survive nutrient limitations. Favored nitrogen sources, particularly ammonium and glutamine, are used preferentially, while the expression of genes required for the use of various secondary nitrogen sources is subject to a regulatory mechanism called nitrogen metabolite repression. Studies on gene regulation in response to nitrogen availability were carried out first in Saccharomyces cerevisiae, Aspergillus nidulans, and Neurospora crassa. These studies revealed that fungi respond to changes in nitrogen availability with physiological and morphological alterations and activation of differentiation processes. In all fungal species studied, the major GATA transcription factor AreA and its co-repressor Nmr are central players of the nitrogen regulatory network. In addition to growth and development, the quality and quantity of nitrogen also affects the formation of a broad range of secondary metabolites (SMs). Recent studies, mainly on species of the genus Fusarium, revealed that AreA does not only regulate a large set of nitrogen catabolic genes, but can also be involved in regulating production of SMs. Furthermore, several other regulators, e.g., a second GATA transcription factor, AreB, that was proposed to negatively control nitrogen catabolic genes by competing with AreA for binding to GATA elements, was shown to act as activator of some nitrogen-repressed as well as nitrogen-induced SM gene clusters. This review highlights our latest understanding of canonical (AreA-dependent) and non-canonical nitrogen regulation mechanisms by which fungi may regulate biosynthesis of certain SMs in response to nitrogen availability.

Keywords: AreA; AreB; GS; MeaB; Nmr1; nitrogen regulation; secondary metabolites.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Model of the nitrogen regulation of secondary metabolism in Fusarium fujikuroi. (A) Under nitrogen-limiting conditions, the intracellular glutamine (Gln) pool is low (light square). This nitrogen status of the cell is probably sensed by the GS and/or additional nitrogen sensors, e.g., the ammonium permease MepB. Under these conditions, the activity of TOR is low and areA is highly expressed. AreA subsequently activates the expression of areB. Both GATA transcription factors, AreA and AreB, are essential for the activation of the GA and probably also the fumonisin gene clusters. Active AreA represses the transcription of the negatively acting bZIP transcription factor MeaBL resulting in high expression of the AreA-independent bikaverin gene cluster. AreA also induces the expression of a variety of genes including nmr, glnA, and mepB. Increasing levels of Nmr interact with AreA thereby putatively modifying its activity by a feed-back loop. (B) Under nitrogen sufficient conditions, TOR is active resulting in activation of the cell cycle. Rapamycin inhibits TOR activity resulting in partial derepression of nitrogen-repressed SM genes. The high intracellular Gln pool (dark blue square) is putatively sensed by the GS and/or other sensors and results in low areA mRNA levels. The AreA-dependent ammonium permease MepB and the general amino acid permease (Gap) are only slowly expressed, but other amino acid permeases (AAPs) and substrate-specific nitrogen transporters facilitate transport of nitrogen into the cell. The decreased level of active AreA leads to reduced GA (and fumonisin) gene expression and induction of meaBL expression. MeaBL itself is involved in repression of bikaverin (BIK) gene expression. The remaining levels of AreB directly or indirectly activate the expression of the nitrogen-induced fusaric acid (FA) and apicidin F (APF) gene clusters (modified after Wiemann and Tudzynski, 2013).

Similar articles

Cited by

References

    1. Abbas A., Valez H., Dobson A. D. (2009). Analysis of the effect of nutritional factors on OTA and OTB biosynthesis and polyketide synthase gene expression in Aspergillus ochraceus. Int. J. Food Microbiol. 135 22–27 10.1016/j.ijfoodmicro.2009.07.014 - DOI - PubMed
    1. Amaike S., Affeldt K. J., Yin W.-B., Franke S., Choithani A., Keller N. P. (2013). The bZIP protein MeaB mediates virulence attributes in Aspergillus flavus. PLoS ONE 8:e74030 10.1371/journal.pone.0074030 - DOI - PMC - PubMed
    1. Andrianopoulos A., Kourambas S., Sharp J. A., Davis M. A., Hynes M. J. (1998). Characterization of the Aspergillus nidulans nmrA gene involved in nitrogen metabolite repression. J. Bacteriol. 180 1973–1977. - PMC - PubMed
    1. Arst H. N., Jr., Cove D. J. (1973). Nitrogen metabolite repression in Aspergillus nidulans. Mol. Gen. Genet. 126 111–141 10.1007/BF00330988 - DOI - PubMed
    1. Bannister A. J., Kouzarides T. (2011). Regulation of chromatin by histone modifications. Cell Res. 21 381–395 10.1038/cr.2011.22 - DOI - PMC - PubMed

LinkOut - more resources