Metabolism of dihydrouracil in Rhodosporidium toruloides

Davis, Cralen; Putnam, M D; Thwaites, William M.

doi:10.1128/jb.158.1.347-350.1984

Cited by 4 publications

(13 citation statements)

References 24 publications

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“…Dihydrouracil and uracil participate in pyrimidine metabolism pathway (belong to ''nucleotide metabolism''), where 5,6-dihydrouracil and NADP+ are catalyzed by dihydropyrimidine dehydrogenase (DPD) to form uracil and NADPH+H+ [14,27]. They are also co-mentioned in many PubMed Abstracts such as [28,29,30,31,32,33,34,35,36,37]. Another two interactive compounds -dihydrouracil and dihydrothymine share a very similar structure, the only difference is that dihydrothymine has a methyl at the 5th position of the hexatomic ring while dihydrouracil has not [38].…”

Section: Evaluation Results By the 5-fold Cross-validationmentioning

confidence: 99%

Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Chen

Huang

et al. 2011

PLoS ONE

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Given a compound, how can we effectively predict its biological function? It is a fundamentally important problem because the information thus obtained may benefit the understanding of many basic biological processes and provide useful clues for drug design. In this study, based on the information of chemical-chemical interactions, a novel method was developed that can be used to identify which of the following eleven metabolic pathway classes a query compound may be involved with: (1) Carbohydrate Metabolism, (2) Energy Metabolism, (3) Lipid Metabolism, (4) Nucleotide Metabolism, (5) Amino Acid Metabolism, (6) Metabolism of Other Amino Acids, (7) Glycan Biosynthesis and Metabolism, (8) Metabolism of Cofactors and Vitamins, (9) Metabolism of Terpenoids and Polyketides, (10) Biosynthesis of Other Secondary Metabolites, (11) Xenobiotics Biodegradation and Metabolism. It was observed that the overall success rate obtained by the method via the 5-fold cross-validation test on a benchmark dataset consisting of 3,137 compounds was 77.97%, which is much higher than 10.45%, the corresponding success rate obtained by the random guesses. Besides, to deal with the situation that some compounds may be involved with more than one metabolic pathway class, the method presented here is featured by the capacity able to provide a series of potential metabolic pathway classes ranked according to the descending order of their likelihood for each of the query compounds concerned. Furthermore, our method was also applied to predict 5,549 compounds whose metabolic pathway classes are unknown. Interestingly, the results thus obtained are quite consistent with the deductions from the reports by other investigators. It is anticipated that, with the continuous increase of the chemical-chemical interaction data, the current method will be further enhanced in its power and accuracy, so as to become a useful complementary vehicle in annotating uncharacterized compounds for their biological functions.

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Section: Evaluation Results By the 5-fold Cross-validationmentioning

confidence: 99%

Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Chen

Huang

et al. 2011

PLoS ONE

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“…Based on our phylogenetic analysis, it is highly probable that dho genes occur in a wide range of ascomycetes and basidiomycetes (Figure 2). Before this study, DHO activity had only been reported in two publications on the yeast Rhodotorula glutinis (Davis et al 1984;Owaki et al 1986) and no structural gene for DHO had been identi ed.…”

Section: Discussionmentioning

confidence: 99%

“…In the reductive pathway for pyrimidine degradation, dihydropyrimidine dehydrogenases (DPHD) catalyse the reduction of uracil to dihydrouracil, using NAD(P)H + H + as electron donor. c. Dihydrouracil oxidase (DHO), which has only been described in Rhodotorula glutinis (Davis et al 1984;Owaki et al 1986), catalyses oxidation of dihydrouracil with molecular oxygen and forms hydrogen peroxide. Sequence identi ers corresponding to the phyla Basidiomycota, Ascomycota and Mucoromycota are indicated in color.…”

Section: Methodsmentioning

confidence: 99%

“…Relevant genotype Activity DHO activity was previously only reported in two studies on Rhodotorula glutinis (Davis et al 1984;Owaki et al 1986). Since the proteome of R. glutinis is not available from Uniprot, no Ura1-ortholog of this yeast was included in our phylogenetic analysis.…”

Section: Strainmentioning

confidence: 98%

“…Aa dho and Scdho encode dihydrouracil oxidases. The observed oxygen requirement for dihydrouracil oxidation of S. cerevisiae strains expressing Aadho or Scdho raised the possibility that these genes might encode dihydrouracil oxidases (DHO; Figure 1, Davis et al 1984). To test this hypothesis, expression cassettes were introduced in an S. cerevisiae ura1∆ background on multicopy (mc) plasmids.…”

Section: Strainmentioning

confidence: 99%

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Identification of fungal dihydrouracil-oxidase genes by expression in Saccharomyces cerevisiae

Bouwknegt

Vos²,

Ortiz‐Merino³

et al. 2022

Preprint

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Analysis of predicted fungal proteomes revealed a large family of sequences that showed similarity to the Saccharomyces cerevisiae Class-I dihydroorotate dehydrogenase Ura1, which supports synthesis of pyrimidines under aerobic and anaerobic conditions. However, expression of codon-optimised representatives of this gene family, from the ascomycete Alternaria alternata and the basidiomycete Schizophyllum commune, only supported growth of an S. cerevisiae ura1Δ mutant when synthetic media were supplemented with dihydrouracil. A hypothesis that these genes encode NAD(P)+-dependent dihydrouracil dehydrogenases (EC 1.3.1.1 or 1.3.1.2) was rejected based on absence of complementation in anaerobic cultures. Uracil- and thymine-dependent oxygen consumption and hydrogen-peroxide production by cell extracts of S. cerevisiae strains expressing the A. alternata and S. commune genes showed that, instead, they encode active dihydrouracil oxidases (DHO, EC1.3.3.7). DHO catalyses the reaction dihydrouracil + O2 → uracil + H2O2 and was only reported in the yeast Rhodotorula glutinis. No structural gene for DHO was previously identified. DHO-expressing strains were highly sensitive to 5-fluoro-dihydrouracil (5F-dhu) and plasmids bearing expression cassettes for DHO were readily lost during growth on 5F-dhu-containing media. These results show the potential applicability of fungal DHO genes as counter-selectable marker genes for genetic modification of S. cerevisiae and other organisms that lack a native DHO. Further research should explore the physiological significance of this enigmatic and apparently widespread fungal enzyme.

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Identification of fungal dihydrouracil-oxidase genes by expression in Saccharomyces cerevisiae

Bouwknegt

Vos

Ortiz‐Merino

et al. 2022

Antonie van Leeuwenhoek

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Analysis of predicted fungal proteomes revealed a large family of sequences that showed similarity to the Saccharomyces cerevisiae Class-I dihydroorotate dehydrogenase Ura1, which supports synthesis of pyrimidines under aerobic and anaerobic conditions. However, expression of codon-optimised representatives of this gene family, from the ascomycete Alternaria alternata and the basidiomycete Schizophyllum commune, only supported growth of an S. cerevisiae ura1Δ mutant when synthetic media were supplemented with dihydrouracil. A hypothesis that these genes encode NAD(P)+-dependent dihydrouracil dehydrogenases (EC 1.3.1.1 or 1.3.1.2) was rejected based on absence of complementation in anaerobic cultures. Uracil- and thymine-dependent oxygen consumption and hydrogen-peroxide production by cell extracts of S. cerevisiae strains expressing the A. alternata and S. commune genes showed that, instead, they encode active dihydrouracil oxidases (DHO, EC1.3.3.7). DHO catalyses the reaction dihydrouracil + O2 → uracil + H2O2 and was only reported in the yeast Rhodotorula glutinis (Owaki in J Ferment Technol 64:205–210, 1986). No structural gene for DHO was previously identified. DHO-expressing strains were highly sensitive to 5-fluorodihydrouracil (5F-dhu) and plasmids bearing expression cassettes for DHO were readily lost during growth on 5F-dhu-containing media. These results show the potential applicability of fungal DHO genes as counter-selectable marker genes for genetic modification of S. cerevisiae and other organisms that lack a native DHO. Further research should explore the physiological significance of this enigmatic and apparently widespread fungal enzyme.

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Metabolism of dihydrouracil in Rhodosporidium toruloides

Cited by 4 publications

References 24 publications

Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Predicting Biological Functions of Compounds Based on Chemical-Chemical Interactions

Identification of fungal dihydrouracil-oxidase genes by expression in Saccharomyces cerevisiae

Identification of fungal dihydrouracil-oxidase genes by expression in Saccharomyces cerevisiae

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