ArticleArchives of biochemistry and biophysics2007
The gene for cobalamin-independent methionine synthase is essential in Candida albicans: a potential antifungal target.
Article in Archives of biochemistry and biophysics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- Article
- Fungal L-Methionine Biosynthesis Pathway Enzymes and Their Applications in Various Scientific and Commercial Fields.Biomolecules · 2024Review
- Adenylyl-Sulfate Kinase (Met14)-Dependent Cysteine and Methionine Biosynthesis Pathways Contribute Distinctively to Pathobiological Processes in Cryptococcus neoformans.Microbiology spectrum · 2023Article
- Sulfur Metabolism as a Promising Source of New Antifungal Targets.Journal of fungi (Basel, Switzerland) · 2022Review
- Comparative proteomics and variations in extracellular matrix of Candida tropicalis biofilm in response to citral.Protoplasma · 2022Article
- Molecular targets for antifungals in amino acid and protein biosynthetic pathways.Amino acids · 2021Review
- Article
- Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics.Scientific reports · 2019Article
- Gene Essentiality Analyzed bymBio · 2018Article
- Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles.Microorganisms · 2017Article
- Methionine synthase is localized to the nucleus inThe Journal of biological chemistry · 2017Article
- Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant.Infection and immunity · 2016Article
- Interplay between Gliotoxin Resistance, Secretion, and the Methyl/Methionine Cycle in Aspergillus fumigatus.Eukaryotic cell · 2015Article
- Inhibitors of amino acids biosynthesis as antifungal agents.Amino acids · 2015Review
- Serine O-acetyltransferase is important, but not essential for cysteine-methionine synthesis in Fusarium graminearum.World journal of microbiology & biotechnology · 2014Article
- Structure of Candida albicans methionine synthase determined by employing surface residue mutagenesis.Archives of biochemistry and biophysics · 2011Article
- Prediction of the clinical outcome in invasive candidiasis patients based on molecular fingerprints of five anti-Candida antibodies in serum.Molecular & cellular proteomics : MCP · 2011Article
- Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants.Eukaryotic cell · 2010Article
- Threonine biosynthetic genes are essential in Cryptococcus neoformans.Microbiology (Reading, England) · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Methionine synthase catalyzes the transfer of a methyl group from tetrahydrofolate to homocysteine to produce methionine. Although mammalian enzymes are cobalamin-dependent, fungal methionine synthases are cobalamin-independent. The opportunistic pathogen Candida albicans is a diploid and carries two copies of the methionine synthase gene, MET6. Homologous recombination was used to disrupt a single MET6 gene. MET6/met6 knock-outs, deleted with either the URA3 or ARG4 cassette, grew as well as the wild-type strain. However, we were unable to obtain a viable met6/met6 deletion strain, even on media supplemented with exogenous methionine. This suggests that methionine synthase is essential to C. albicans. To explore this further, a C. albicans strain was constructed in which one MET6 locus was deleted and the second placed under a regulatable promoter. The conditional mutant grew well under inducing conditions, even in the absence of methionine. It would not grow under repressing conditions in the absence of methionine, but would grow when the media was supplemented with exogenous methionine. A Western blot showed that a small amount of enzyme was expressed under repressing conditions. Taken together, these data reveal that methionine is necessary for growth of C. albicans, but not sufficient-a minimal level of methionine synthase expression is required, perhaps to limit homocysteine toxicity. Furthermore, these results suggest that cobalamin-independent methionine synthase is a plausible target for the design of antifungal agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.