Regulation of ergosterol biosynthesis and sterol uptake in a sterol-auxotrophic yeast
Open accessAbstract
Inhibition of sterol uptake in Saccharomyces cerevisiae sterol auxotroph FY3 (alpha hem1 erg7 ura) by delta-aminolevulinic acid (ALA) is dependent on the ability of the organism to synthesize heme from ALA. Sterol-depleted cells not exposed to ALA or strain PFY3 cells, with a double heme mutation, exposed to ALA did not exhibit inhibition of sterol uptake. Addition of ALA to sterol-depleted FY3 stimulated production of a high endogenous concentration of 2,3-oxidosqualene (25.55 micrograms mg-1 [dry weight]) at 24 h, whereas FY3 not exposed to ALA or PFY3 exposed to ALA did not accumulate 2,3-oxidosqualene. The high concentration of 2,3-oxidosqualene in FY3 with ALA decreased, and 2,3;22,23-dioxidosqualene increased to a very high level. The elevation of 2,3-oxidosqualene by ALA was correlated with a fivefold increase in the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34). The enhanced activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was prevented by cycloheximide but not chloramphenicol and was dependent on a fermentative energy source. Inhibition of sterol uptake could not be attributed to 2,3-oxidosqualene or 2,3;22,23-dioxidosqualene but was due to a nonsaturating level of ergosterol produced as a consequence of heme competency through a leaky erg7 mutation.
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Essential sterols from engineered yeast prevent honeybee colony population declinePreprint
Moore, E., de Sousa, R. T., Felsinger, S., Arnesen, J. A., Dyekjær, J. D., Farman, D. I., Gonçalves, R. F. S., Stevenson, P. C., Borodina, I., & Wright, G. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.09.627483 · Cited by 1 · see citing works
- Authors
- Lorenz, R. T., & Parks, L. W.
- Affiliations
- North Carolina State University (US)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 1987-08
- Volume
- 169
- Issue
- 8
- Pages
- 3707-3711
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC212455
- OpenAlex
- W1961551106
- Cited by
- 39
- References
- 27
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Bacteriology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (1r01am037222-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- ergosterol biosynthesis, sterol uptake, sterol auxotrophy, Saccharomyces cerevisiae, 5-aminolevulinic acid, heme biosynthesis, 2,3-oxidosqualene, 3-hydroxy-3-methylglutaryl-CoA reductase
- MeSH terms
- Aminolevulinic Acid, Biological Transport, Cholesterol, Ergosterol, Heme, Hydroxymethylglutaryl CoA Reductases, Lipids, Mutation, Saccharomyces cerevisiae, Squalene, Sterols
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