Completing the folate biosynthesis pathway in <i>Plasmodium falciparum</i>: <i>p</i>-aminobenzoate is produced by a highly divergent promiscuous aminodeoxychorismate lyase

Magnani, Giovanni; Lomazzi, Michela; Peracchi, Alessio

doi:10.1042/bj20130896

Cited by 7 publications

(5 citation statements)

References 43 publications

(44 reference statements)

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“…In this study, all the four functionally distinct subfamilies (namely, l-branched chain aminotransferases, d-amino acid aminotransferases, (R)-selective transaminases [RATAs], and 4-amino-4-deoxychorismate lyases [ADCLs]) are found clustered into different clades, as also shown earlier [76,77]. However, for the promiscuous nature of several transaminases [78] and unclear metabolic role of RATAs, the phylogenetic analysis failed to accurately classify two functionally characterized RATA sequences CpuTA1 and MgiTA1, sharing a 49% sequence identity and containing conserved amino acids for both RATAs and ADCLs [75]. This confirms that the initially constructed/ prioritized sequence dataset should have a sufficiently higher number of entries, with ample phylogenetic diversity and minimal redundancy.…”

Section: Strategic Steps To Assess and Achieve Biological Accuracy Of...supporting

confidence: 67%

Refined Evolutionary Trees Through an Exceptionally Compatible Alignment-Substitution Model

Runthala,

Sowmya,

Nasika

et al. 2024

J App Biol Biotech

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A phylogenetic tree commonly represents evolutionary relationships within a set of protein sequences. Various methods and strategies have been used to improve the accuracy of phylogenetic trees, but their capacity to derive a biologically credible relationship appears to be overestimated. Although the quality of the protein sequence alignment and the choice of substitution matrix are preliminary constraints to define the biological accuracy of the overlapped residues, the alignment is not iteratively optimized through the statistical testing of residue-substitution models. The exact alignment protocol and substitution model information are by default used for every sequence set by a server to construct an often-irrelevant phylogenetic tree, and no sequence-based tailoring of phylogenetic strategy is implemented by any server. Rigorously constructing 270 evolutionary trees, constructed using IQ-TREE based on 13 different alignments (Clustal-Omega, Kalign, MAFFT, MUSCLE, TCoffee, and Promals3D, as well as their HHPred-based hidden Markov model [HMM] alignments using HHPred) and nine substitution models (Dayhoff, JJT, block substitution matrix62, WAG, probability matrix from blocks [PMB], direct computation with mutability [DCMUT], JTTDCmut, LG, and variable time), the present study highlights the failure of the current methods and emphasizes the need for a more accurate scrutiny of the entire phylogenetic methodology. MUSCLE alignment and the LG and Dayhoff matrices yield more accurate phylogenetic results for sequences shorter than 500 residues for the log-likelihood measure. Moreover, Kalign 1 HMM alignment yields the top-ranked tree with the lowest tree length score with only the PMB matrix, making this substitution model more accurate in terms of total tree length score. The suggested strategy would be beneficial for understanding the potential pitfalls of phylogenetic inference and would aid us in deriving a more accurate evolutionary relationship for a sequence dataset.

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Section: Strategic Steps To Assess and Achieve Biological Accuracy Of...supporting

confidence: 67%

Refined Evolutionary Trees Through an Exceptionally Compatible Alignment-Substitution Model

Runthala,

Sowmya,

Nasika

et al. 2024

J App Biol Biotech

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“…The ubiquitous expression of ADCL suggests additional functions, especially during mosquito stages (Figure 1B). A previous study demonstrated a substantial secondary aminotransferase activity of Plasmodium falciparum ADCL, which was suggested as contributing to the detoxification of exogenous D-amino acids (Magnani et al, 2013).…”

Section: Resultsmentioning

confidence: 96%

“…It is believed that chorismate, which is produced via the shikimate pathway (Roberts et al, 1998), is converted to pABA in a two-step reaction (Figure 1A). A potential aminodeoxychorismate synthase (ADCS, PBANKA_0823300) and an aminodeoxychorismate lyase (ADCL, PBANKA_1322100) are predicted by Plasmodium genome sequences (Magnani et al, 2013;Salcedo-Sora and Ward, 2013;Triglia and Cowman, 1999). However, their roles in Plasmodium folate metabolism during infection remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium Para-Aminobenzoate Synthesis and Salvage Resolve Avoidance of Folate Competition and Adaptation to Host Diet

et al. 2019

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“…Nevertheless, a physiological role could not be assigned to the AtDAT1 encoding gene in plants to date. Most interestingly, the homolog of AtDAT1 in Plasmodium falciparum also displays such a dual function and the ADCL activity is repressed by D-AAs (Magnani et al, 2013). Loss-of-function mutants of AtDAT1 showed almost identical defects as Ler in D-AA metabolism, with D-Met as strongest effector.…”

Section: Introductionmentioning

confidence: 99%

AtDAT1 Is a Key Enzyme of D-Amino Acid Stimulated Ethylene Production in Arabidopsis thaliana

et al. 2019

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D-Enantiomers of proteinogenic amino acids (D-AAs) are found ubiquitously, but the knowledge about their metabolism and functions in plants is scarce. A long forgotten phenomenon in this regard is the D-AA-stimulated ethylene production in plants. As a starting point to investigate this effect, the Arabidopsis accession Landsberg erecta (Ler) got into focus as it was found defective in metabolizing D-AAs. Combining genetics and molecular biology of T-DNA insertion lines and natural variants together with biochemical and physiological approaches, we could identify AtDAT1 as a major D-AA transaminase in Arabidopsis. Atdat1 loss-of-function mutants and Arabidopsis accessions with defective AtDAT1 alleles were unable to produce the metabolites of D-Met, D-Ala, D-Glu, and L-Met. This result corroborates the biochemical characterization, which showed highest activity of AtDAT1 using D-Met as a substrate. Germination of seedlings in light and dark led to enhanced growth inhibition of atdat1 mutants on D-Met. Ethylene measurements revealed an increased D-AA stimulated ethylene production in these mutants. According to initial working models of this phenomenon, D-Met is preferentially malonylated instead of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). This decrease of ACC degradation should then lead to the increase of ethylene production. We could observe a reciprocal relation of malonylated methionine and ACC upon D-Met application and significantly more malonyl-methionine in atdat1 mutants. Unexpectedly, the malonyl-ACC levels did not differ between mutants and wild type. With AtDAT1, the first central enzyme of plant D-AA metabolism was characterized biochemically and physiologically. The specific effects of D-Met on ACC metabolism, ethylene production, and plant development of dat1 mutants unraveled the impact of AtDAT1 on these processes; however, they are not in full accordance to previous working models. Instead, our results imply the influence of additional factors or processes on D-AA-stimulated ethylene production, which await to be uncovered.

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Completing the folate biosynthesis pathway in Plasmodium falciparum: p-aminobenzoate is produced by a highly divergent promiscuous aminodeoxychorismate lyase

Cited by 7 publications

References 43 publications

Refined Evolutionary Trees Through an Exceptionally Compatible Alignment-Substitution Model

Refined Evolutionary Trees Through an Exceptionally Compatible Alignment-Substitution Model

Plasmodium Para-Aminobenzoate Synthesis and Salvage Resolve Avoidance of Folate Competition and Adaptation to Host Diet

AtDAT1 Is a Key Enzyme of D-Amino Acid Stimulated Ethylene Production in Arabidopsis thaliana

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