Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism

Viridiana Olin-Sandoval, Jason Shu Lim Yu, Leonor Miller-Fleming, Mohammad Tauqeer Alam, Stephan Kamrad, Clara Correia-Melo, Robert Haas, Joanna Segal, David Alejandro Peña Navarro, Lucia Herrera-Dominguez, Oscar Méndez-Lucio, Jakob Vowinckel, Michael Mülleder and Markus Ralser ()
Additional contact information
Viridiana Olin-Sandoval: University of Cambridge
Jason Shu Lim Yu: The Francis Crick Institute
Leonor Miller-Fleming: University of Cambridge
Mohammad Tauqeer Alam: University of Warwick
Stephan Kamrad: The Francis Crick Institute
Clara Correia-Melo: The Francis Crick Institute
Robert Haas: University of Cambridge
Joanna Segal: The Francis Crick Institute
David Alejandro Peña Navarro: BOKU - University of Natural Resources and Life Sciences
Lucia Herrera-Dominguez: The Francis Crick Institute
Oscar Méndez-Lucio: Universidad Nacional Autónoma de México
Jakob Vowinckel: University of Cambridge
Michael Mülleder: University of Cambridge
Markus Ralser: University of Cambridge

Nature, 2019, vol. 572, issue 7768, 249-253

Abstract: 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 Tpo1p3–5 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.

Date: 2019
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DOI: 10.1038/s41586-019-1442-6

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