Characterization, heterologous expression and functional analysis of mevalonate diphosphate decarboxylase gene (MVD) of Candida albicans

Dassanayake, R. S., Cao, L., Samaranayake, L. P. and Berges, T. (2002) Characterization, heterologous expression and functional analysis of mevalonate diphosphate decarboxylase gene (MVD) of Candida albicans. Molecular Genetics and Genomics, 267 3: 281-290. doi:10.1007/s00438-002-0648-7


Author Dassanayake, R. S.
Cao, L.
Samaranayake, L. P.
Berges, T.
Title Characterization, heterologous expression and functional analysis of mevalonate diphosphate decarboxylase gene (MVD) of Candida albicans
Formatted title
Characterization, heterologous expression and functional analysis of mevalonate diphosphate decarboxylase gene (MVD) of Candida albicans
Journal name Molecular Genetics and Genomics   Check publisher's open access policy
ISSN 1617-4615
1617-4623
Publication date 2002-05-01
Sub-type Article (original research)
DOI 10.1007/s00438-002-0648-7
Open Access Status Not yet assessed
Volume 267
Issue 3
Start page 281
End page 290
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
Mevalonate diphosphate decarboxylase (MVD) catalyzes the conversion of mevalonate diphosphate to isopentenyl diphosphate, a key building block for a large family of functionally important biomolecules. We have cloned the gene encoding MVD from Candida albicans, and report the first characterization of such a gene from an opportunistic fungal pathogen. Sequence analysis revealed that the MVD comprises 362 amino acid residues with a predicted molecular weight of 39.5 kDa, sharing minimal identity with the human analogue. Analysis of the genomic sequence indicated that the coding frame is interrupted by a small intron of 51 bp. Southern analysis of genomic DNA demonstrated that MVD is a single-copy gene. Furthermore, Southern analysis of electrophoretic karyotypes of C. albicans obtained by pulsed-field gel electrophoresis showed that MVD is located on chromosome 1. Northern analysis revealed that the level of MVD expression is affected by (1) the carbon source in the growth medium, (2) the growth phase, and (3) the growth form of the fungus (yeast-like or hyphal). To demonstrate the biological function of C. albicans MVD, complementation experiments were carried out with an S. cerevisiae strain (erg19ts) that is temperature-sensitive for MVD activity. A single copy of the C. albicans MVD gene, under the control of the NOP1 promoter, was able fully to complement the erg19ts phenotype, and expression of the epitope-tagged C. albicans MVD was detectable by Western analysis. Furthermore, the low degree of sequence identity between C. albicans MVD and its human analogue raises the possibility that fungal-specific inhibitors can be developed for the enzyme. Thus, C. albicans MVD appears to be an interesting candidate that could be targeted for the development of anti-fungal agents.
Keyword Candida albicans
Complementation
Mevalonate diphosphate decarboxylase
Saccharomyces cerevisiae
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Dentistry Publications
 
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