Fresh insights into the pyrimidine metabolism in the trypanosomatids

Tiwari, Kartikeya; Dubey, Vikash Kumar

doi:10.1186/s13071-018-2660-8

Cited by 19 publications

(20 citation statements)

References 91 publications

(106 reference statements)

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“…In this regard, it is somewhat unexpected that only two enzymes (adenylosuccinate synthetase (ADSS) and inosine monophosphate dehydrogenase (IMPDH)) were identified in the L. tarentolae glycosomal proteome, and five of these enzymes were identified in the glycosomal fractions of L. donovani. Similarly, we identified most of the enzymes constituting the de novo pyrimidine biosynthesis pathway (Table 4) [59] in the L. infantum proteome, whereas Jamdhade et al [57] only found one enzyme of this pathway in the L. donovani glycosomal proteome-the orotate phosphoribosyltransferase (LDBPK_160560). All the enzymes (grey squares) that are required to complete the pathway were identified in this study.…”

Section: Components Of the Proteostasis Networkmentioning

confidence: 72%

The Experimental Proteome of Leishmania infantum Promastigote and Its Usefulness for Improving Gene Annotations

Sanchiz

Morato

Rastrojo

et al. 2020

Genes

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Leishmania infantum causes visceral leishmaniasis (kala-azar), the most severe form of leishmaniasis, which is lethal if untreated. A few years ago, the re-sequencing and de novo assembling of the L. infantum (JPCM5 strain) genome was accomplished, and now we aimed to describe and characterize the experimental proteome of this species. In this work, we performed a proteomic analysis from axenic cultured promastigotes and carried out a detailed comparison with other Leishmania experimental proteomes published to date. We identified 2352 proteins based on a search of mass spectrometry data against a database built from the six-frame translated genome sequence of L. infantum. We detected many proteins belonging to organelles such as glycosomes, mitochondria, or flagellum, as well as many metabolic enzymes and many putative RNA binding proteins and molecular chaperones. Moreover, we listed some proteins presenting post-translational modifications, such as phosphorylations, acetylations, and methylations. On the other hand, the identification of peptides mapping to genomic regions previously annotated as non-coding allowed for the correction of annotations, leading to the N-terminal extension of protein sequences and the uncovering of eight novel protein-coding genes. The alliance of proteomics, genomics, and transcriptomics has resulted in a powerful combination for improving the annotation of the L. infantum reference genome.

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Section: Components Of the Proteostasis Networkmentioning

confidence: 72%

The Experimental Proteome of Leishmania infantum Promastigote and Its Usefulness for Improving Gene Annotations

Sanchiz

Morato

Rastrojo

et al. 2020

Genes

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“…In fungi, a similar protein exists but lacks the dihydroorotase function, while in bacteria, archaea, and other eukaryotes, the first three reactions of the pathway are carried out by three separate proteins [96]. In trypanosomatids, these are also catalyzed by three independent enzymes, which in some species form multiprotein complexes [96,99].…”

Section: Nucleotide Metabolismmentioning

confidence: 99%

“…In trypanosomatids, the last step of the UMP biosynthesis is catalyzed by a glycosomal bifunctional enzyme comprised of orotate phosphoribosyltransferase (OPRT) and orotidine 5′-monophosphate decarboxylase (OMPDC) fused in the reverse order (pyrF/E, or OPRT/OMPDC) as compared to its metazoan counterpart called uridine-monophosphate synthase (UMPS; pyrE/F, or OMPDC/OPRT) [99]. Euglenozoa show a complex pattern of UMP synthesis, since we have identified separate transcripts encoding pyrF and pyrE genes, as well as their fusions (Additional file 9: Table S7).…”

Section: Nucleotide Metabolismmentioning

confidence: 99%

Evolution of metabolic capabilities and molecular features of diplonemids, kinetoplastids, and euglenids

et al. 2020

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Background: The Euglenozoa are a protist group with an especially rich history of evolutionary diversity. They include diplonemids, representing arguably the most species-rich clade of marine planktonic eukaryotes; trypanosomatids, which are notorious parasites of medical and veterinary importance; and free-living euglenids. These different lifestyles, and particularly the transition from free-living to parasitic, likely require different metabolic capabilities. We carried out a comparative genomic analysis across euglenozoan diversity to see how changing repertoires of enzymes and structural features correspond to major changes in lifestyles. Results: We find a gradual loss of genes encoding enzymes in the evolution of kinetoplastids, rather than a sudden decrease in metabolic capabilities corresponding to the origin of parasitism, while diplonemids and euglenids maintain more metabolic versatility. Distinctive characteristics of molecular machines such as kinetochores and the pre-replication complex that were previously considered specific to parasitic kinetoplastids were also identified in their free-living relatives. Therefore, we argue that they represent an ancestral rather than a derived state, as thought until the present. We also found evidence of ancient redundancy in systems such as NADPH-dependent thiol-redox. Only the genus Euglena possesses the combination of trypanothione-, glutathione-, and thioredoxin-based systems supposedly present in the euglenozoan common ancestor, while other representatives of the phylum have lost one or two of these systems. Lastly, we identified convergent losses of specific metabolic capabilities between free-living kinetoplastids and ciliates. Although this observation requires further examination, it suggests that certain eukaryotic lineages are predisposed to such convergent losses of key enzymes or whole pathways. Conclusions: The loss of metabolic capabilities might not be associated with the switch to parasitic lifestyle in kinetoplastids, and the presence of a highly divergent (or unconventional) kinetochore machinery might not be restricted to this protist group. The data derived from the transcriptomes of free-living early branching prokinetoplastids suggests that the pre-replication complex of Trypanosomatidae is a highly divergent version of the conventional machinery. Our findings shed light on trends in the evolution of metabolism in protists in general and open multiple avenues for future research.

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“…In this regards, it is somewhat unexpected that only two enzymes (ADSS and IMPDH) were identified in the L. tarentolae glycosomal proteome, and five of these enzymes in the glycosomal fractions of L. donovani. Similarly, we have identified in the L. infantum proteome most of the enzymes constituting the de novo pyrimidine biosynthesis pathway (Table 4) [59], whereas Jamdhade et al [57], in the L. donovani glycosomal proteome, only found one enzyme of this pathway, the orotate phosphoribosyltransferase (LDBPK_160560). Peer-reviewed version available at Genes 2020, 11, 1036; doi:10.3390/genes11091036…”

Section: Glycosomal Proteins Represent a Substantial Fraction Of The mentioning

confidence: 66%

The Experimental Proteome of Leishmania infantum promastigote and Its Usefulness for Improving Gene Annotations

Sanchiz¹,

Morato²,

Rastrojo³

et al. 2020

Preprint

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Leishmania infantum is causative of visceral leishmaniasis (kala-azar), the most severe form of leishmaniasis, lethal if untreated. Few years ago, re-sequencing and de novo assembling of the L. infantum (strain JPCM5) genome was accomplished, and now we aimed to describe and characterize the experimental proteome of this species. In this work, we have performed a proteomic analysis from axenic cultured promastigotes and carried out a detailed comparison with other Leishmania experimental proteomes published to date. We identified 2,352 proteins based on the search of mass spectrometry data against a database built from the six-frame translated genome sequence of L. infantum. We have detected many proteins belonging to organelles such as glycosomes, mitochondria or flagellum, as well as many metabolic enzymes, and a large number of putative RNA binding proteins and molecular chaperones. Moreover, we listed the proteins presenting post-translational modifications, such as phosphorylations, acetylations and methylations, among others. On the other hand, the identification of peptides mapping to genomic regions previously annotated as non-coding has allowed to correct annotations, leading to N-terminal extension of protein sequences, and the uncovering of eight novel protein-coding genes. The alliance of proteomics, genomics and transcriptomics has resulted in a powerful combination for improving the L. infantum reference genome annotation.

show abstract

Fresh insights into the pyrimidine metabolism in the trypanosomatids

Cited by 19 publications

References 91 publications

The Experimental Proteome of Leishmania infantum Promastigote and Its Usefulness for Improving Gene Annotations

The Experimental Proteome of Leishmania infantum Promastigote and Its Usefulness for Improving Gene Annotations

Evolution of metabolic capabilities and molecular features of diplonemids, kinetoplastids, and euglenids

The Experimental Proteome of Leishmania infantum promastigote and Its Usefulness for Improving Gene Annotations

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