A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity
Summary: Adipic acid production by yeast fermentation is gaining attention as a renewable source of platform chemicals for making nylon products. However, adipic acid toxicity inhibits yeast growth and fermentation. Here, we performed a chemogenomic screen in Saccharomyces cerevisiae to understand t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221002959 |
| _version_ | 1823929788046245888 |
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| author | Eugene Fletcher Kevin Mercurio Elizabeth A. Walden Kristin Baetz |
| author_facet | Eugene Fletcher Kevin Mercurio Elizabeth A. Walden Kristin Baetz |
| author_sort | Eugene Fletcher |
| collection | DOAJ |
| description | Summary: Adipic acid production by yeast fermentation is gaining attention as a renewable source of platform chemicals for making nylon products. However, adipic acid toxicity inhibits yeast growth and fermentation. Here, we performed a chemogenomic screen in Saccharomyces cerevisiae to understand the cellular basis of adipic acid toxicity. Our screen revealed that KGD1 (a key gene in the tricarboxylic acid cycle) deletion improved tolerance to adipic acid and its toxic precursor, catechol. Conversely, disrupting ergosterol biosynthesis as well as protein trafficking and vacuolar transport resulted in adipic acid hypersensitivity. Notably, we show that adipic acid disrupts the Membrane Compartment of Can1 (MCC) on the plasma membrane and impacts endocytosis. This was evidenced by the rapid internalization of Can1 for vacuolar degradation. As ergosterol is an essential component of the MCC and protein trafficking mechanisms are required for endocytosis, we highlight the importance of these cellular processes in modulating adipic acid toxicity. |
| first_indexed | 2024-12-16T21:14:18Z |
| format | Article |
| id | doaj.art-63da561d21b64135a85e520d9e7fcb51 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T21:14:18Z |
| publishDate | 2021-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-63da561d21b64135a85e520d9e7fcb512022-12-21T22:16:06ZengElsevieriScience2589-00422021-04-01244102327A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicityEugene Fletcher0Kevin Mercurio1Elizabeth A. Walden2Kristin Baetz3Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, CanadaOttawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, CanadaOttawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, CanadaOttawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Corresponding authorSummary: Adipic acid production by yeast fermentation is gaining attention as a renewable source of platform chemicals for making nylon products. However, adipic acid toxicity inhibits yeast growth and fermentation. Here, we performed a chemogenomic screen in Saccharomyces cerevisiae to understand the cellular basis of adipic acid toxicity. Our screen revealed that KGD1 (a key gene in the tricarboxylic acid cycle) deletion improved tolerance to adipic acid and its toxic precursor, catechol. Conversely, disrupting ergosterol biosynthesis as well as protein trafficking and vacuolar transport resulted in adipic acid hypersensitivity. Notably, we show that adipic acid disrupts the Membrane Compartment of Can1 (MCC) on the plasma membrane and impacts endocytosis. This was evidenced by the rapid internalization of Can1 for vacuolar degradation. As ergosterol is an essential component of the MCC and protein trafficking mechanisms are required for endocytosis, we highlight the importance of these cellular processes in modulating adipic acid toxicity.http://www.sciencedirect.com/science/article/pii/S2589004221002959Cell BiologySystems Biology |
| spellingShingle | Eugene Fletcher Kevin Mercurio Elizabeth A. Walden Kristin Baetz A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity iScience Cell Biology Systems Biology |
| title | A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| title_full | A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| title_fullStr | A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| title_full_unstemmed | A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| title_short | A yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| title_sort | yeast chemogenomic screen identifies pathways that modulate adipic acid toxicity |
| topic | Cell Biology Systems Biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221002959 |
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