Versatility of putative aromatic aminotransferases from Candida albicans

Rząd, Kamila; Milewski, Sławomir; Gabriel, Iwona

doi:10.1016/j.fgb.2017.11.009

Cited by 11 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it should be pointed out that the K m of L-kynurenine of AroH is 5 to 20-fold higher than that for aromatic substrates. Finally, the finding that AroH displays the highest catalytic efficiency toward α-ketoadipate suggests that the enzyme could be also involved in lysine metabolism, as recently reported for orthologs from Candida albicans (Rzad et al, 2018 ).…”

Section: Resultssupporting

confidence: 61%

“…Among the aro genes, aroH (Afu2g13630) encodes a putative pyridoxal 5'-phosphate (PLP)-dependent aromatic aminotransferase, which transaminates L-tryptophan to generate indolepyruvate. AroH shows the highest sequence identity (~50%) with Aro8 of S. cerevisiae as well as with Aro8 recently characterized in Candida albicans , an opportunistic yeast often diagnosed in immunocompromised hosts (Rao et al, 2010 ; Rzad et al, 2018 ). C. albicans Aro8 is definitely the most versatile enzyme among the aminotransferases already investigated.…”

Section: Introductionmentioning

confidence: 74%

“…A detailed study on the main genes playing a role in A. fumigatus virulence, does not include Aro proteins (Abad et al, 2010 ). Nevertheless, it is widely accepted that the catalytic versatility of aminotransferases plays a key role in the adaptation and survival of pathogenic fungi in the changing environment of the host by allowing the growth using different nitrogen sources (Rzad et al, 2018 ). Therefore, fungal aminotransferases may constitute a basis for the nutritional flexibility in the fungus Aspergillus , and the characterization of Aros enzymes may be pivotal for drug design of innovative therapies targeting fungal metabolic check points.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biochemical Characterization of Aspergillus fumigatus AroH, a Putative Aromatic Amino Acid Aminotransferase

Dindo

Costanzi

Pieroni

et al. 2018

Front. Mol. Biosci.

View full text Add to dashboard Cite

The rise in the frequency of nosocomial infections is becoming a major problem for public health, in particular in immunocompromised patients. Aspergillus fumigatus is an opportunistic fungus normally present in the environment directly responsible for lethal invasive infections. Recent results suggest that the metabolic pathways related to amino acid metabolism can regulate the fungus-host interaction and that an important role is played by enzymes involved in the catabolism of L-tryptophan. In particular, in A. fumigatus L-tryptophan regulates Aro genes. Among them, AroH encodes a putative pyridoxal 5'-phosphate-dependent aminotransferase. Here we analyzed the biochemical features of recombinant purified AroH by spectroscopic and kinetic analyses corroborated by in silico studies. We found that the protein is dimeric and tightly binds the coenzyme forming a deprotonated internal aldimine in equilibrium with a protonated ketoenamine form. By setting up a new rapid assay method, we measured the kinetic parameters for the overall transamination of substrates and we demonstrated that AroH behaves as an aromatic amino acid aminotransferase, but also accepts L-kynurenine and α-aminoadipate as amino donors. Interestingly, computational approaches showed that the predicted overall fold and active site topology of the protein are similar to those of its yeast ortholog, albeit with some differences in the regions at the entrance of the active site, which could possibly influence substrate specificity. Should targeting fungal metabolic adaptation be of therapeutic value, the results of the present study may pave the way to the design of specific AroH modulators as potential novel agents at the host/fungus interface.

show abstract

Section: Resultssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biochemical Characterization of Aspergillus fumigatus AroH, a Putative Aromatic Amino Acid Aminotransferase

Dindo

Costanzi

Pieroni

et al. 2018

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…In the common gut bacterium Clostridium sporogenes , Trp transamination by AroAT is the first step for the production of various metabolically active compounds including indole pyruvic acid, which accumulates in the host serum and probably mediates the microbe–host interactions regulating immune, metabolic, and neuronal responses [ 43 , 63 ]. In fungi, the Aro8 gene encodes a versatile PLP-dependent AroAT whose metabolic role is shared between the lysine synthesis by the aminoadipate pathway and the catabolism of aromatic amino acids [ 64 , 65 ]. In C. albicans , Aro8 is a very versatile enzyme active against L-histidine, L-lysine, and aromatic amino acids [ 64 ].…”

Section: A Biochemical Overview Of Microbial and Host Trp-metabolimentioning

confidence: 99%

Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism

Cellini

Zelante

Dindo

et al. 2020

IJMS

View full text Add to dashboard Cite

The chemical processes taking place in humans intersects the myriad of metabolic pathways occurring in commensal microorganisms that colonize the body to generate a complex biochemical network that regulates multiple aspects of human life. The role of tryptophan (Trp) metabolism at the intersection between the host and microbes is increasingly being recognized, and multiple pathways of Trp utilization in either direction have been identified with the production of a wide range of bioactive products. It comes that a dysregulation of Trp metabolism in either the host or the microbes may unbalance the production of metabolites with potential pathological consequences. The ability to redirect the Trp flux to restore a homeostatic production of Trp metabolites may represent a valid therapeutic strategy for a variety of pathological conditions, but identifying metabolic checkpoints that could be exploited to manipulate the Trp metabolic network is still an unmet need. In this review, we put forward the hypothesis that pyridoxal 5′-phosphate (PLP)-dependent enzymes, which regulate multiple pathways of Trp metabolism in both the host and in microbes, might represent critical nodes and that modulating the levels of vitamin B6, from which PLP is derived, might represent a metabolic checkpoint to re-orienteer Trp flux for therapeutic purposes.

show abstract

“…To better understand why PG38 grew better than PG6 at neutral pH, the 236 genes differentially expressed between both strains at this pH (S7B Table) were also analysed for enriched GO-terms ( Fig 6B; 12 contributed to 5 GO-terms enrichment). This analysis highlighted 'transaminase activity', 'oxidoreductase activity' and 'peroxisomal part', for which details of the genes driving enrichment are presented in the S8B Table. Thus, the overexpression of the gene encoding an aromatic amino acid aminotransferase could play a role in the adaptation and survival of PG38 in the changing environment by allowing the growth using different nitrogen sources [36]. In order to survive in different and rapidly changing environments, the fungi must indeed be able to adapt via their expression of genes for amino acid metabolism since amino acids constitute key sources of nitrogen for growth of many fungi.…”

Section: Plos Onementioning

confidence: 99%

pH effect on strain-specific transcriptomes of the take-all fungus

Gazengel¹,

Lebreton²,

Lapalu³

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

The soilborne fungus Gaeumannomyces tritici (G. tritici) causes the take-all disease on wheat roots. Ambient pH has been shown to be critical in different steps of G. tritici life cycle such as survival in bulk soil, saprophytic growth, and pathogenicity on plants. There are however intra-specific variations and we previously found two types of G. tritici strains that grow preferentially either at acidic pH or at neutral/alkaline pH; gene expression involved in pH-signal transduction pathway and pathogenesis was differentially regulated in two strains representative of these types. To go deeper in the description of the genetic pathways and the understanding of this adaptative mechanism, transcriptome sequencing was achieved on two strains (PG6 and PG38) which displayed opposite growth profiles in two pH conditions (acidic and neutral). PG6, growing better at acidic pH, overexpressed in this condition genes related to cell proliferation. In contrast, PG38, which grew better at neutral pH, overexpressed in this condition genes involved in fatty acids and amino acid metabolisms, and genes potentially related to pathogenesis. This strain also expressed stress resistance mechanisms at both pH, to assert a convenient growth under various ambient pH conditions. These differences in metabolic pathway expression between strains at different pH might buffer the effect of field or soil variation in wheat fields, and explain the success of the pathogen.

show abstract

Versatility of putative aromatic aminotransferases from Candida albicans

Cited by 11 publications

References 40 publications

Biochemical Characterization of Aspergillus fumigatus AroH, a Putative Aromatic Amino Acid Aminotransferase

Biochemical Characterization of Aspergillus fumigatus AroH, a Putative Aromatic Amino Acid Aminotransferase

Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism

pH effect on strain-specific transcriptomes of the take-all fungus

Contact Info

Product

Resources

About