Synthesis of Dolichols in <i>Candida albicans</i> Is Co-Regulated with Elongation of Fatty Acids
Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. Dolichols are α-saturated polyprenols, and their saturation in <i>S. cerevisiae</i> is catalyzed by polyprenyl reductase Dfg10 together with some other unknown enzymes. The aim of this study was to identify such...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/1/409 |
| Summary: | Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. Dolichols are α-saturated polyprenols, and their saturation in <i>S. cerevisiae</i> is catalyzed by polyprenyl reductase Dfg10 together with some other unknown enzymes. The aim of this study was to identify such enzymes in <i>Candida</i>. The Dfg10 polyprenyl reductase from <i>S. cerevisiae</i> comprises a C-terminal 3-oxo-5-alpha-steroid 4-dehydrogenase domain. Alignment analysis revealed such a domain in two ORFs (orf19.209 and orf19.3293) from <i>C. albicans</i>, which were similar, respectively, to Dfg10 polyprenyl reductase and Tsc13 enoyl-transferase from <i>S. cerevisiae</i>. Deletion of orf19.209 in <i>Candida</i> impaired saturation of polyprenols. The Tsc13 homologue turned out not to be capable of saturating polyprenols, but limiting its expression reduce the cellular level of dolichols and polyprenols. This reduction was not due to a decreased expression of genes encoding <i>cis</i>-prenyltransferases from the dolichol branch but to a lower expression of genes encoding enzymes of the early stages of the mevalonate pathway. Despite the resulting lower consumption of acetyl-CoA, the sole precursor of the mevalonate pathway, it was not redirected towards fatty acid synthesis or elongation. Lowering the expression of <i>TSC13</i> decreased the expression of the <i>ACC1</i> gene encoding acetyl-CoA carboxylase, the key regulatory enzyme of fatty acid synthesis and elongation. |
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| ISSN: | 1661-6596 1422-0067 |