title: Adaptive Evolution of Phosphorus Metabolism inProchlorococcus.
abstract: Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacteriumProchlorococcus marinusthrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794 reactions involving 680 metabolites distributed in 6 subcellular locations.iJC568 was used to quantify metabolic fluxes under PLG conditions, and we observed a close correspondence between experimental and computed fluxes. We found that MED4 has minimized its dependence on intracellular phosphate, not only through drastic depletion of phosphorus-containing biomass components but also through network-wide reductions in phosphate-reaction participation and the loss of a key enzyme, succinate dehydrogenase. These alterations occur despite the stringency of having relatively few pathway redundancies and an extremely high proportion of essential metabolic genes (47%; defined as the percentage of lethalin silicogene knockouts). These strategies are examples of nutrient-controlled adaptive evolution and confer a dramatic growth rate advantage to MED4 in phosphorus-limited regions.IMPORTANCEMicrobes are known to employ three basic strategies to compete for limiting elemental resources: (i) cell quotas may be adjusted by alterations to cell physiology or by substitution of a more plentiful resource, (ii) stressed cells may synthesize high-affinity transporters, and (iii) cells may access more costly sources from internal stores, by degradation, or by petitioning other microbes. In the case of phosphorus, a limiting resource in vast oceanic regions, the cosmopolitan cyanobacteriumProchlorococcus marinusthrives by adopting all three strategies and a fourth, previously unknown strategy. By generating a detailed model of its metabolism, we found that strain MED4 has evolved a way to reduce its dependence on phosphate by minimizing the number of enzymes involved in phosphate transformations, despite the stringency of nearly half of its metabolic genes being essential for survival. Relieving phosphorus limitation, both physiologically and throughout intermediate metabolism, substantially improves phosphorus-specific growth rates.
authors.affiliation: Daniel K. Inouye Center for Microbial Oceanography, Research and Education, School of Ocean and Earth Science and Technology, University of Hawaii, Honolulu, Hawaii, USA.
authors.forename: John R
authors.identifier: 0000-0002-8630-0551
authors.initials: JR
authors.lastname: Casey
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Adil
authors.initials: A
authors.lastname: Mardinoglu
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Daniel K. Inouye Center for Microbial Oceanography, Research and Education, School of Ocean and Earth Science and Technology, University of Hawaii, Honolulu, Hawaii, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Karl
keywords: Prochlorococcus; evolution of metabolic networks; flux balance analysis; metabolic modeling; phosphorus metabolism; succinate dehydrogenase