Two Aspergillus nidulans genes encoding methylenetetrahydrofolate reductases are up-regulated by homocysteine

SUMMARYThe genusTrichodermacontains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for “hot topic” research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism inT. reesei,T. atroviride, andT. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of eachTrichodermaspecies discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved inN-linked glycosylation was detected, as were indications for the ability ofTrichodermaspp. to generate hybrid galactose-containingN-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique toTrichoderma, and these warrant further investigation. We found interesting expansions in theTrichodermagenus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique toT. atrovirideis the duplication of the alternative sulfur amino acid synthesis pathway.

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“…Such organization is also observed in other filamentous fungi, like N. crassa and A. nidulans (431)(432)(433). Similarly, Trichoderma spp.…”

Section: Sulfur Metabolismmentioning

confidence: 55%

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Schmoll

Dattenböck

Carreras-Villaseñor

et al. 2016

Microbiol Mol Biol Rev

163

195

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“…For example, ZmMET1 was downregulated by cold stress in maize (Ohba et Expression of the DNA MTase family in rice al., 2000). In Arabidopsis, the transcription level of MET1 is at least 10,000 times more than that of MET11 (Sieńko et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive gene expression analysis of the DNA (cytosine-5) methyltransferase family in rice (Oryza sativa L.)

Ahmad¹,

Huang²,

Lan³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Cytosine DNA methylation is a conserved epigenetic regulatory mechanism in both plants and animals. DNA methyltransferases (DNA MTases) not only initiate (de novo) but also maintain the process of DNA methylation. Here, we characterized the genome-wide expression profiles of 10 cytosine DNA MTase genes belonging to 4 subfamilies, MET1, CMT, DNMT2, and DRM, in rice. Tissue-specific gene expression analysis showed that all family members varied widely in their expression and specificities and might be involved in some basic metabolic pathways. Similarly, the expression of all rice cytosine DNA MTase genes was not regulated by plant hormones except OsDRM1a and OsDRM1b, which were downregulated by jasmonic acid. The transcription level of 10 genes in rice shoots and roots was also measured under salt and osmotic stress. Meanwhile, quantitative polymerase chain reaction data of the japonica and indica rice cultivars revealed that there is large variation in the expression activities of all genes. The results provide a foundation to further explore the roles of DNA MTases and the epigenetic regulation of abiotic stress responses in rice.

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“…However, of special significance, the abundance of the cobalamin-independent methionine synthase MetH/D (AFUA_4G07360) was significantly increased (1.9-to 2.2-fold), and that of MTHFR/MtrA was significantly increased (1.8-fold), in response to gliotoxin exposure. Both of these enzymes are essential for methionine biosynthesis (37,38) and for the operation of the methyl/methionine cycle, which affects SAM biosynthesis.…”

Section: Resultsmentioning

confidence: 99%

“…In fungi, the production of methionine from Hcy is catalyzed by MetH/D, and in Candida albicans, this enzyme has been shown to be essential for cell viability (37). Indeed, Hcy induces the upregulation of A. nidulans methionine synthase (51), in addition to the positive regulation of MTHFR/MtrA expression (38). Interestingly, a significantly increased abundance of MTHFR/MtrA This model is in accordance with all experimental observations whereby exogenous and/or endogenous gliotoxin results in GT-(SH) 2 formation followed by conversion to gliotoxin and secretion via GliA.…”

Section: Integrated Systems In Aspergillus Fumigatusmentioning

confidence: 99%

Interplay between Gliotoxin Resistance, Secretion, and the Methyl/Methionine Cycle in Aspergillus fumigatus

et al. 2015

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Mechanistic studies on gliotoxin biosynthesis and self-protection in Aspergillus fumigatus, both of which require the gliotoxin oxidoreductase GliT, have revealed a rich landscape of highly novel biochemistries, yet key aspects of this complex molecular architecture remain obscure. Here we show that an A. fumigatus ⌬gliA strain is completely deficient in gliotoxin secretion but still retains the ability to efflux bisdethiobis(methylthio)gliotoxin (BmGT). This correlates with a significant increase in sensitivity to exogenous gliotoxin because gliotoxin trapped inside the cell leads to (i) activation of the gli cluster, as disabling gli cluster activation, via gliZ deletion, attenuates the sensitivity of an A. fumigatus ⌬gliT strain to gliotoxin, thus implicating cluster activation as a factor in gliotoxin sensitivity, and (ii) increased methylation activity due to excess substrate (dithiol gliotoxin) for the gliotoxin bis-thiomethyltransferase GtmA. Intracellular dithiol gliotoxin is oxidized by GliT and subsequently effluxed by GliA. In the absence of GliA, gliotoxin persists in the cell and is converted to BmGT, with levels significantly higher than those in the wild type. Similarly, in the ⌬gliT strain, gliotoxin oxidation is impeded, and methylation occurs unchecked, leading to significant S-adenosylmethionine (SAM) depletion and S-adenosylhomocysteine (SAH) overproduction. This in turn significantly contributes to the observed hypersensitivity of gliT-deficient A. fumigatus to gliotoxin. Our observations reveal a key role for GliT in preventing dysregulation of the methyl/methionine cycle to control intracellular SAM and SAH homeostasis during gliotoxin biosynthesis and exposure. Moreover, we reveal attenuated GliT abundance in the A. fumigatus ⌬gliK strain, but not the ⌬gliG strain, following exposure to gliotoxin, correlating with relative sensitivities. Overall, we illuminate new systems interactions that have evolved in gliotoxin-producing, compared to gliotoxin-naive, fungi to facilitate their cellular presence. Biosynthesis, self-protection mechanisms, and functionality of gliotoxin and related epidithiodiketopiperazine (ETP) molecular species, such as chaetocin and acetylaranotin, are attracting ever-increasing attention as a consequence of findings from highthroughput genome sequencing projects, application of gene deletion technologies, and mass spectrometric analytical methodologies (1-5). Indeed, existing paradigms of gliotoxin (Fig. 1) as a toxin and the perspective of the disulfide bridge-containing (oxidized) form as the final, or only, product are undergoing significant reconsideration (6-11).Self-protection against disulfide-containing metabolites appears to be essential in both fungi and bacteria. It has been demonstrated that the gliotoxin oxidoreductase GliT (12), encoded within the gli cluster, protects Aspergillus fumigatus against exogenous gliotoxin and is essential for gliotoxin biosynthesis (12, 13). A similar mechanism for self-protection against holomycin in Streptomyces clavulige...

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Two Aspergillus nidulans genes encoding methylenetetrahydrofolate reductases are up-regulated by homocysteine

Cited by 12 publications

References 31 publications

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

Comprehensive gene expression analysis of the DNA (cytosine-5) methyltransferase family in rice (Oryza sativa L.)

Interplay between Gliotoxin Resistance, Secretion, and the Methyl/Methionine Cycle in Aspergillus fumigatus

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