Abstract
Living organisms have evolved mechanisms for adjusting their metabolism to adapt to environmental nutrient availability. Terrestrial animals utilize the ornithine–urea cycle to dispose of excess nitrogen derived from dietary protein. Here, we identified an active ornithine–ammonia cycle (OAC) in cyanobacteria through an approach combining dynamic 15N and 13C tracers, metabolomics, and mathematical modeling. The pathway starts with carbamoyl phosphate synthesis by the bacterial- and plant-type glutamine-dependent enzyme and ends with conversion of arginine to ornithine and ammonia by a novel arginine dihydrolase. An arginine dihydrolase–deficient mutant showed disruption of OAC and severely impaired cell growth when nitrogen availability oscillated. We demonstrated that the OAC allows for rapid remobilization of nitrogen reserves under starvation and a high rate of nitrogen assimilation and storage after the nutrient becomes available. Thus, the OAC serves as a conduit in the nitrogen storage-and-remobilization machinery in cyanobacteria and enables cellular adaptation to nitrogen fluctuations.
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Acknowledgements
The authors thank Y. Shan for technical assistance on hybrid quadrupole-orbitrap MS and J. Zhao for helpful discussions. This work was funded for C.Y. by the National Natural Science Foundation of China (31630003 and 31470168), the National Key R&D Program of China (2016YFC1303303), and the Chinese Academy of Sciences (XDPB0400).
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H.Z. performed most experiments and wrote the manuscript. Y.L. conducted biochemical assays. X.N. performed bioinformatics. L.L. contributed LC–MS analysis. Q.H. contributed mathematical modeling. G.-P.Z. contributed experimental design and discussion. C.Y. designed experiments, analyzed data, and wrote the manuscript.
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Zhang, H., Liu, Y., Nie, X. et al. The cyanobacterial ornithine–ammonia cycle involves an arginine dihydrolase. Nat Chem Biol 14, 575–581 (2018). https://doi.org/10.1038/s41589-018-0038-z
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DOI: https://doi.org/10.1038/s41589-018-0038-z
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