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Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism
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Olin-Sandoval, Viridiana, Yu, Jason Shu Lim, Miller-Fleming, Leonor, Alam, Mohammad T., Kamrad, Stephan, Correia-Melo, Clara, Haas, Robert, Segal, Joanna, Peña Navarro, David Alejandro, Herrera-Dominguez, Lucia, Méndez-Lucio, Oscar, Vowinckel, Jakob, Mülleder, Michael and Ralser, Markus (2019) Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism. Nature, 572 (7768). pp. 249-253. doi:10.1038/s41586-019-1442-6
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WRAP-lysine-harvesting-antioxidant-strategy-triggers-underground-polyamine-metabolism-Alam-2019.pdf - Accepted Version - Requires a PDF viewer. Download (2907Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/s41586-019-1442-6
Abstract
Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway—a conserved first-line response to oxidative insults1,2. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p3,4,5 in maintaining oxidant resistance is unknown6. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH—which would otherwise be required for lysine biosynthesis—is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.
| Item Type: | Journal Article | |||||||||||||||||||||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QK Botany Q Science > QR Microbiology |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Lysine, Lysine -- Synthesis -- Inhibitors, Microbial diversity, Chemical inhibitors, Polyamines , Plants -- Effect of stress on -- Molecular aspects | |||||||||||||||||||||||||||
| Journal or Publication Title: | Nature | |||||||||||||||||||||||||||
| Publisher: | Nature Publishing | |||||||||||||||||||||||||||
| ISSN: | 0028-0836 | |||||||||||||||||||||||||||
| Official Date: | 8 August 2019 | |||||||||||||||||||||||||||
| Dates: |
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| Volume: | 572 | |||||||||||||||||||||||||||
| Number: | 7768 | |||||||||||||||||||||||||||
| Page Range: | pp. 249-253 | |||||||||||||||||||||||||||
| DOI: | 10.1038/s41586-019-1442-6 | |||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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