Phosphatidylserine synthesis is essential for viability of the human fungal pathogen Cryptococcus neoformans
Phospholipids are an integral part of the cellular membrane structure and can be produced by a de novo biosynthetic pathway and, alternatively, by the Kennedy pathway. Studies in several yeast species have shown that the phospholipid phosphatidylserine (PS) is synthesized from CDP-diacylglycerol and...
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/105546 http://hdl.handle.net/10220/47823 |
| _version_ | 1811680230673219584 |
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| author | Konarzewska, Paulina Wang, Yina Han, Gil-Soo Goh, Kwok Jian Gao, Yong-Gui Carman, George M. Xue, Chaoyang |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Konarzewska, Paulina Wang, Yina Han, Gil-Soo Goh, Kwok Jian Gao, Yong-Gui Carman, George M. Xue, Chaoyang |
| author_sort | Konarzewska, Paulina |
| collection | NTU |
| description | Phospholipids are an integral part of the cellular membrane structure and can be produced by a de novo biosynthetic pathway and, alternatively, by the Kennedy pathway. Studies in several yeast species have shown that the phospholipid phosphatidylserine (PS) is synthesized from CDP-diacylglycerol and serine, a route that is different from its synthesis in mammalian cells, involving a base-exchange reaction from preexisting phospholipids. Fungal-specific PS synthesis has been shown to play an important role in fungal virulence and has been proposed as an attractive drug target. However, PS synthase, which catalyzes this reaction, has not been studied in the human fungal pathogen Cryptococcus neoformans. Here, we identified and characterized the PS synthase homolog (Cn Cho1) in this fungus. Heterologous expression of Cn CHO1 in a Saccharomyces cerevisiae cho1Δ mutant rescued the mutant's growth defect in the absence of ethanolamine supplementation. Moreover, an Sc cho1Δ mutant expressing Cn CHO1 had PS synthase activity, confirming that the Cn CHO1 encodes PS synthase. We also found that PS synthase in C. neoformans is localized to the endoplasmic reticulum and that it is essential for mitochondrial function and cell viability. Of note, its deficiency could not be complemented by ethanolamine or choline supplementation for the synthesis of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) via the Kennedy pathway. These findings improve our understanding of phospholipid synthesis in a pathogenic fungus and indicate that PS synthase may be a useful target for antifungal drugs. |
| first_indexed | 2024-10-01T03:21:45Z |
| format | Journal Article |
| id | ntu-10356/105546 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:21:45Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1055462023-02-28T17:05:35Z Phosphatidylserine synthesis is essential for viability of the human fungal pathogen Cryptococcus neoformans Konarzewska, Paulina Wang, Yina Han, Gil-Soo Goh, Kwok Jian Gao, Yong-Gui Carman, George M. Xue, Chaoyang School of Biological Sciences Phospholipid Metabolism DRNTU::Science::Biological sciences Phosphatidylserine Phospholipids are an integral part of the cellular membrane structure and can be produced by a de novo biosynthetic pathway and, alternatively, by the Kennedy pathway. Studies in several yeast species have shown that the phospholipid phosphatidylserine (PS) is synthesized from CDP-diacylglycerol and serine, a route that is different from its synthesis in mammalian cells, involving a base-exchange reaction from preexisting phospholipids. Fungal-specific PS synthesis has been shown to play an important role in fungal virulence and has been proposed as an attractive drug target. However, PS synthase, which catalyzes this reaction, has not been studied in the human fungal pathogen Cryptococcus neoformans. Here, we identified and characterized the PS synthase homolog (Cn Cho1) in this fungus. Heterologous expression of Cn CHO1 in a Saccharomyces cerevisiae cho1Δ mutant rescued the mutant's growth defect in the absence of ethanolamine supplementation. Moreover, an Sc cho1Δ mutant expressing Cn CHO1 had PS synthase activity, confirming that the Cn CHO1 encodes PS synthase. We also found that PS synthase in C. neoformans is localized to the endoplasmic reticulum and that it is essential for mitochondrial function and cell viability. Of note, its deficiency could not be complemented by ethanolamine or choline supplementation for the synthesis of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) via the Kennedy pathway. These findings improve our understanding of phospholipid synthesis in a pathogenic fungus and indicate that PS synthase may be a useful target for antifungal drugs. Published version 2019-03-15T06:16:53Z 2019-12-06T21:53:19Z 2019-03-15T06:16:53Z 2019-12-06T21:53:19Z 2019 Journal Article Konarzewska, P., Wang, Y., Han, G.-S., Goh, K. J., Gao, Y.-G., Carman, G. M., & Xue, C. (2019). Phosphatidylserine synthesis is essential for viability of the human fungal pathogen Cryptococcus neoformans. Journal of Biological Chemistry, 294(7), 2329-2339. doi:10.1074/jbc.RA118.006738 0021-9258 https://hdl.handle.net/10356/105546 http://hdl.handle.net/10220/47823 10.1074/jbc.RA118.006738 en Journal of Biological Chemistry © 2019 American Society for Biochemistry and Molecular Biology. All rights reserved. This paper was published in Journal of Biological Chemistry and is made available with permission of American Society for Biochemistry and Molecular Biology. 12 p. application/pdf |
| spellingShingle | Phospholipid Metabolism DRNTU::Science::Biological sciences Phosphatidylserine Konarzewska, Paulina Wang, Yina Han, Gil-Soo Goh, Kwok Jian Gao, Yong-Gui Carman, George M. Xue, Chaoyang Phosphatidylserine synthesis is essential for viability of the human fungal pathogen Cryptococcus neoformans |
| title | Phosphatidylserine synthesis is essential for viability of the human fungal pathogen
Cryptococcus neoformans |
| title_full | Phosphatidylserine synthesis is essential for viability of the human fungal pathogen
Cryptococcus neoformans |
| title_fullStr | Phosphatidylserine synthesis is essential for viability of the human fungal pathogen
Cryptococcus neoformans |
| title_full_unstemmed | Phosphatidylserine synthesis is essential for viability of the human fungal pathogen
Cryptococcus neoformans |
| title_short | Phosphatidylserine synthesis is essential for viability of the human fungal pathogen
Cryptococcus neoformans |
| title_sort | phosphatidylserine synthesis is essential for viability of the human fungal pathogen cryptococcus neoformans |
| topic | Phospholipid Metabolism DRNTU::Science::Biological sciences Phosphatidylserine |
| url | https://hdl.handle.net/10356/105546 http://hdl.handle.net/10220/47823 |
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