Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Role of nitric oxide and flavohemoglobin homolog genes in Aspergillus nidulans sexual development and mycotoxin production.

ABSTRACT: Flavohemoglobins are widely distributed in both prokaryotes and eukaryotes. These proteins are involved in reducing nitric oxide levels. Deletion of the Aspergillus nidulans flavohemoglobin gene fhbA induced sexual development and decreased sterigmatocystin production. Supplementation with a nitric oxide-releasing compound promoted cleistothecial formation and increased nsdD and steA expression, indicating that nitric oxide induces sexual development. This is the first study on the effect of nitric oxide on morphogenesis and secondary metabolism in fungi.

SUBMITTER: Baidya S

PROVIDER: S-EPMC3147476 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Role of nitric oxide and flavohemoglobin homolog genes in Aspergillus nidulans sexual development and mycotoxin production.

Baidya Sachin S Cary Jeffrey W JW Grayburn W Scott WS Calvo A M AM

Applied and environmental microbiology 20110603 15

Flavohemoglobins are widely distributed in both prokaryotes and eukaryotes. These proteins are involved in reducing nitric oxide levels. Deletion of the Aspergillus nidulans flavohemoglobin gene fhbA induced sexual development and decreased sterigmatocystin production. Supplementation with a nitric oxide-releasing compound promoted cleistothecial formation and increased nsdD and steA expression, indicating that nitric oxide induces sexual development. This is the first study on the effect of nit ...[more]

PMID: 21642398

Similar Datasets

Aspergillus nidulans verA is required for production of the mycotoxin sterigmatocystin.

Project description:Aspergillus nidulans produces the carcinogenic mycotoxin sterigmatocystin (ST), the next-to-last precursor in the aflatoxin (AF) biosynthetic pathway found in the closely related fungi Aspergillus flavus and Aspergillus parasiticus. We identified and characterized an A. nidulans gene, verA, that is required for converting the AF precursor versicolorin A to ST. verA is closely related to several polyketide biosynthetic genes involved in polyketide production in Streptomyces spp. and exhibits extended sequence similarity to A. parasiticus ver-1, a gene proposed to encode an enzyme involved in converting versicolorin A to ST. By performing a sequence analysis of the region 3' to verA, we identified two additional open reading frames, designated ORF1 and ORF2. ORF2 is closely related to a number of cytochrome P-450 monooxygenases, while ORF1 shares identity with the gamma subunit of translation elongation factor 1. Given that several steps in the ST-AF pathway may require monooxygenase activity and that AF biosynthetic genes are clustered in A. flavus and A. parasiticus, we suggest that verA may be part of a cluster of genes required for ST biosynthesis. We disrupted the verA coding region by inserting the A. nidulans argB gene into the center of the coding region and transformed an A. nidulans argB2 mutant to arginine prototrophy. Seven transformants that produced DNA patterns indicative of a verA disruption event were grown under ST-inducing conditions, and all of the transformants produced versicolorin A but negligible amounts of ST (200-fold to almost 1,000-fold less than the wild type), confirming the hypothesis that verA encodes an enzyme necessary for converting versicolorin A to ST.

| S-EPMC201501 | biostudies-other

cpsA regulates mycotoxin production, morphogenesis and cell wall biosynthesis in the fungus Aspergillus nidulans.

Project description:The model fungus Aspergillus nidulans synthesizes numerous secondary metabolites, including sterigmatocystin (ST). The production of this toxin is positively controlled by the global regulator veA. In the absence of veA (ΔveA), ST biosynthesis is blocked. Previously, we performed random mutagenesis in a ΔveA strain and identified revertant mutants able to synthesize ST, among them RM1. Complementation of RM1 with a genomic library revealed that the mutation occurred in a gene designated as cpsA. While in the ΔveA genetic background cpsA deletion restores ST production, in a veA wild-type background absence of cpsA reduces and delays ST biosynthesis decreasing the expression of ST genes. Furthermore, cpsA is also necessary for the production of other secondary metabolites, including penicillin, affecting the expression of PN genes. In addition, cpsA is necessary for normal asexual and sexual development. Chemical and microscopy analyses revealed that CpsA is found in cytoplasmic vesicles and it is required for normal cell wall composition and integrity, affecting adhesion capacity and oxidative stress sensitivity. The conservation of cpsA in Ascomycetes suggests that cpsA homologs might have similar roles in other fungal species.

| S-EPMC5506848 | biostudies-literature

The Aspergillus nidulans Pbp1 homolog is required for normal sexual development and secondary metabolism.

Project description:P bodies and stress granules are RNA-containing structures governing mRNA degradation and translational arrest, respectively. Saccharomyces cerevisiae Pbp1 protein localizes to stress granules and promotes their formation and is involved in proper polyadenylation, suppression of RNA-DNA hybrids, and preventing aberrant rDNA recombination. A genetic screen for Aspergillus nidulans mutants aberrant in secondary metabolism identified the Pbp1 homolog, PbpA. Using Dcp1 (mRNA decapping) as a marker for P-body formation and FabM (Pab1, poly-A binding protein) to track stress granule accumulation, we examine the dynamics of RNA granule formation in A. nidulans cells lacking pub1, edc3, and pbpA. Although PbpA acts as a functional homolog of yeast PBP1, PbpA had little impact on either P-body or stress granule formation in A. nidulans in contrast to Pub1 and Edc3. However, we find that PbpA is critical for sexual development and its loss increases the production of some secondary metabolites including the carcinogen sterigmatocystin.

| S-EPMC5337145 | biostudies-literature

Allostery in the nitric oxide dioxygenase mechanism of flavohemoglobin.

Project description:The substrates O2 and NO cooperatively activate the NO dioxygenase function of Escherichia coli flavohemoglobin. Steady-state and transient kinetic measurements support a structure-based mechanistic model in which O2 and NO movements and conserved amino acids at the E11, G8, E2, E7, B10, and F7 positions within the globin domain control activation. In the cooperative and allosteric mechanism, O2 migrates to the catalytic heme site via a long hydrophobic tunnel and displaces LeuE11 away from the ferric iron, which forces open a short tunnel to the catalytic site gated by the ValG8/IleE15 pair and LeuE11. NO permeates this tunnel and leverages upon the gating side chains triggering the CD loop to furl, which moves the E and F-helices and switches an electron transfer gate formed by LysF7, GlnE7, and water. This allows FADH2 to reduce the ferric iron, which forms the stable ferric-superoxide-TyrB10/GlnE7 complex. This complex reacts with internalized NO with a bimolecular rate constant of 1010 M-1 s-1 forming nitrate, which migrates to the CD loop and unfurls the spring-like structure. To restart the cycle, LeuE11 toggles back to the ferric iron. Actuating electron transfer with O2 and NO movements averts irreversible NO poisoning and reductive inactivation of the enzyme. Together, structure snapshots and kinetic constants provide glimpses of intermediate conformational states, time scales for motion, and associated energies.

| S-EPMC7948479 | biostudies-literature

Transcriptome analysis of nitrate assimilation in Aspergillus nidulans reveals connections to nitric oxide metabolism.

Project description:Nitrate is a dominant form of inorganic nitrogen (N) in soils and can be efficiently assimilated by bacteria, fungi and plants. We studied here the transcriptome of the short-term nitrate response using assimilating and non-assimilating strains of the model ascomycete Aspergillus nidulans. Among the 72 genes positively responding to nitrate, only 18 genes carry binding sites for the pathway-specific activator NirA. Forty-five genes were repressed by nitrate metabolism. Because nirA(-) strains are N-starved at nitrate induction conditions, we also compared the nitrate transcriptome with N-deprived conditions and found a partial overlap of differentially regulated genes between these conditions. Nitric oxide (NO)-metabolizing flavohaemoglobins were found to be co-regulated with nitrate assimilatory genes. Subsequent molecular characterization revealed that the strongly inducible FhbA is required for full activity of nitrate and nitrite reductase enzymes. The co-regulation of NO-detoxifying and nitrate/nitrite assimilating systems may represent a conserved mechanism, which serves to neutralize nitrosative stress imposed by an external NO source in saprophytic and pathogenic fungi. Our analysis using membrane-permeable NO donors suggests that signalling for NirA activation only indirectly depends on the nitrate transporters NrtA (CrnA) and NrtB (CrnB).

| S-EPMC3020322 | biostudies-literature

Bacterial flavohemoglobin: a molecular tool to probe mammalian nitric oxide biology.

Project description:A wide range of mammalian signaling and stress pathways are mediated by nitric oxide (NO), which is synthesized in vivo by the nitric oxide synthase (NOS) family of enzymes. Experimental manipulations of NO are frequently achieved by either inhibition or activation of endogenous NOS or via providing exogenous NO sources. On the contrary, many microbes consume NO via flavohemoglobin (FlavoHb), a highly efficient NO-dioxygenase that protects from nitrosative stress. Here we report a novel resource for studying NO in mammalian cells by heterologously expressing Escherichia coli FlavoHb within a lentiviral delivery system. This technique boosts endogenous cellular consumption of NO, thus providing a simple and efficacious approach to studying mammalian NO biology that can be employed as both a primary experimental and confirmatory tool.

| S-EPMC3096140 | biostudies-literature

A critical role for staphylococcal nitric oxide synthase in controlling flavohemoglobin toxicity.

Project description:Most coagulase-negative staphylococcal species, including the opportunistic pathogen Staphylococcus epidermidis, struggle to maintain redox homeostasis and grow under nitrosative stress. Under these conditions, growth can only resume once nitric oxide (NO) is detoxified by the flavohemoglobin Hmp. Paradoxically, S. epidermidis produces endogenous NO through its genetically encoded nitric oxide synthase (seNOS) and heavily relies on its activity for growth. In this study, we investigate the basis of the growth advantage attributed to seNOS activity. Our findings reveal that seNOS supports growth by countering Hmp toxicity. S. epidermidis relies on Hmp activity for its survival in the host under NO stress. However, in the absence of nitrosative stress, Hmp generates significant amounts of the harmful superoxide radical (O2•-) from its heme prosthetic group which impedes growth. To limit Hmp toxicity, nitrite (NO2-) derived from seNOS promotes CymR-CysK regulatory complex activity, which typically regulates cysteine metabolism, but we now demonstrate to also repress hmp transcription. These findings reveal a critical mechanism through which the bacterial NOS-Hmp axis drives staphylococcal fitness.

| S-EPMC10594633 | biostudies-literature

VelC positively controls sexual development in Aspergillus nidulans.

Project description:Fungal development and secondary metabolism is intimately associated via activities of the fungi-specific velvet family proteins including VeA, VosA, VelB and VelC. Among these, VelC has not been characterized in Aspergillus nidulans. In this study, we characterize the role of VelC in asexual and sexual development in A. nidulans. The velC mRNA specifically accumulates during the early phase of sexual development. The deletion of velC leads to increased number of conidia and reduced production of sexual fruiting bodies (cleistothecia). In the velC deletion mutant, mRNA levels of the brlA, abaA, wetA and vosA genes that control sequential activation of asexual sporulation increase. Overexpression of velC causes increased formation of cleistothecia. These results suggest that VelC functions as a positive regulator of sexual development. VelC is one of the five proteins that physically interact with VosA in yeast two-hybrid and GST pull down analyses. The ΔvelC ΔvosA double mutant produced fewer cleistothecia and behaved similar to the ΔvosA mutant, suggesting that VosA is epistatic to VelC in sexual development, and that VelC might mediate control of sex through interacting with VosA at specific life stages for sexual fruiting.

| S-EPMC3938535 | biostudies-literature

Nitric Oxide-Mediated Induction of Dispersal in Pseudomonas aeruginosa Biofilms Is Inhibited by Flavohemoglobin Production and Is Enhanced by Imidazole.

Project description:The biological signal molecule nitric oxide (NO) was found to induce biofilm dispersal across a range of bacterial species, which led to its consideration for therapeutic strategies to treat biofilms and biofilm-related infections. However, biofilms are often not completely dispersed after exposure to NO. To better understand this phenomenon, we investigated the response of Pseudomonas aeruginosa biofilm cells to successive NO treatments. When biofilms were first pretreated with a low, noneffective dose of NO, a second dose of the signal molecule at a concentration usually capable of inducing dispersal did not have any effect. Amperometric analysis revealed that pretreated P. aeruginosa cells had enhanced NO-scavenging activity, and this effect was associated with the production of the flavohemoglobin Fhp. Further, quantitative real-time reverse transcription-PCR (qRT-PCR) analysis showed that fhp expression increased by over 100-fold in NO-pretreated biofilms compared to untreated biofilms. Biofilms of mutant strains harboring mutations in fhp or fhpR, encoding a NO-responsive regulator of fhp, were not affected in their dispersal response after the initial pretreatment with NO. Overall, these results suggest that FhpR can sense NO to trigger production of the flavohemoglobin Fhp and inhibit subsequent dispersal responses to NO. Finally, the addition of imidazole, which can inhibit the NO dioxygenase activity of flavohemoglobin, attenuated the prevention of dispersal after NO pretreatment and improved the dispersal response in older, starved biofilms. This study clarifies the underlying mechanisms of impaired dispersal induced by repeated NO treatments and offers a new perspective for improving the use of NO in biofilm control strategies.

| S-EPMC5826158 | biostudies-literature

The Rim15p homolog RimO mediates starvation response and is required for secondary metabolite production in Aspergillus nidulans

Project description:Depending on the prevailing environmental, developmental and nutritional conditions Aspergillus nidulans produces different combinations of secondary metabolites (SMs). To activate the biosynthetic gene cluster (BGC) for a given SM global, chromatin-based de-repression must be integrated with pathway-specific induction signals. Here we describe a new global regulator affecting the set of starvation-induced SMs. We found a hitherto uncharacterized putative PAS-domain containing kinase to be upregulated in SM-producing cultures. The predicted protein is highly similar to yeast Rim15 which transmits nutritional and stress signals to downstream effectors involved in chromatin regulation, stress and starvation response. The putative kinase – termed RimO – is required for the transcription of a number of starvation-induced SMs including sterigmatocystin (ST). RimO regulates the pathway-specific transcription factor AflR both at the transcriptional and post-translational level. In the absence of RimO aflR is barely transcribed under SM conditions and the protein is not retained in the nucleus. Genome-wide transcriptional profiling showed that cells lacking rimO fail to correctly respond to carbon and nitrogen starvation and continue to transcribe genes of the basic metabolism to a high level. Conversely, overexpression of the kinase made cells largely insensitive to glucose repression and led to overproduction of several secondary metabolites. We propose a model that positions RimO downstream of PKA being necessary to transmit the starvation signal to downstream targets, including chromatin and transcriptional regulators of SM gene clusters. Additionally, it may also regulate signaling modules required for recognizing the starvation response.

2022-03-01 | GSE184618 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data