title: pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism.
abstract: Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ≈8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3 (-) into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools.
authors.affiliation: Department of Applied Mathematics, University of Washington, Seattle, WA 98195;
authors.forename: Niall M
authors.identifier: 0000-0002-3491-8341
authors.initials: NM
authors.lastname: Mangan
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Avi
authors.initials: A
authors.lastname: Flamholz
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Hood
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; Department of Chemistry, University of California, Berkeley, CA 94720 savage@berkeley.edu.
authors.forename: David F
authors.identifier: 0000-0003-0042-2257
authors.initials: DF
authors.lastname: Savage
mesh_terms: D001692:Biological Transport / Q000235:genetics; D002244:Carbon / Q000378:metabolism; D057486:Carbon Cycle / Q000235:genetics / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D000458:Cyanobacteria / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D010788:Photosynthesis / Q000235:genetics*; D012273:Ribulose-Bisphosphate Carboxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D002245:Carbon Dioxide; D002244:Carbon; D012273:Ribulose-Bisphosphate Carboxylase; D002256:Carbonic Anhydrases
keywords: RuBisCO; carbon fixation; cyanobacteria; inorganic carbon; systems biology