Cloning of the Rhizomucor miehei 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene and its heterologous expression in Mucor circinelloides
Abstract
In this study, the gene hmgR encoding the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) was cloned and characterized in the zygomycete fungus Rhizomucor miehei. The hmgR gene comprises a total of 3,585 bp including the coding sequence of a 1,058 amino acids length putative protein and five introns (137, 83, 59, 60 and 69 bp in length) dispersed in the whole coding region. Southern hybridization analysis revealed that the gene is present only in one copy in the R. miehei genome. The isolated Rhizomucor gene was expressed in the related fungus, Mucor circinelloides. Transformants harbouring the Rhizomucor hmgR gene in an autoreplicative plasmid proved to be more tolerant to statins (e.g. lovastatin, simvastatin, and fluvastatin), the competitive inhibitors of the HMG-CoA reductase, than the original M. circinelloides strain. At the same time, heterologous expression of the Rhizomucor hmgR did not affect the carotenoid production of M. circinelloides.
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Lukács et al. demonstrated that increased hmgR gene dose by transformation decreased sensitivity to statins in M. circinelloides.
“Lukács et al. have elegantly demonstrated a decreased sensitivity to statins in M. circinelloides when the hmgR gene dose became increased by transformation.22”
Lukács et al. described distinct sensitivity to statins in Mucor circinelloides, with MIC values in the order of those reported here and fluvastatin much more effective than lovastatin and simvastatin.
“Distinct sensitivity to statins was also described by Lukács et al. in Mucor circinelloides, 22 with MIC values in the order of those herein reported and being fluvastatin much more effective than lovastatin and simvastatin.”
Controversy in statin susceptibility data may be due to differences in applied methodology and strains.
“Controversy is frequently observed when comparing statins susceptibility data.That may be due to differences in the applied methodology and the strains involved.22”
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- Authors
- Lukács, G., Papp, T., Somogyvári, F., Csernetics, Á., Nyilasi, I., & Vágvölgyi, C.
- Affiliations
- University of Szeged (HU)
- Corresponding author
- Papp, Tamás
- Venue
- Antonie van Leeuwenhoek
- Published
- 2008-10-14
- Volume
- 95
- Issue
- 1
- Pages
- 55-64
- ISSN
- 0003-6072 (ISSN-L)
- 1572-9699
- OpenAlex
- W1982386942
- Cited by
- 19
- References
- 41
- Citations by year
- 2023: 3 · 2022: 1 · 2019: 3 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Antonie van Leeuwenhoek (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- Rhizomucor miehei, Mucor circinelloides, HMG-CoA reductase, gene cloning, heterologous expression, lovastatin, simvastatin, fluvastatin, carotenoid production, introns
- MeSH terms
- Amino Acid Sequence, Cloning, Molecular, Fungal Proteins, Fungi, Molecular Sequence Data, Mucor, Phylogeny, Gene Expression, Sequence Alignment, Protein Structure, Tertiary, Rhizomucor, Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent
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