Trichodesmium, the predominant marine diazotrophic cyanobacterium, concurrently performs nitrogen (N2) fixation and photosynthesis, the latter of which produces oxygen (O2) that inhibits N2 fixation. Hopanoid lipids in Trichodesmium may play a role in dynamically regulating membrane permeability to O2, potentially alleviating O2 stress on N2 fixation. However, the physiological impacts of this dynamic permeability are not well understood. We developed a model showing that dynamically modulating membrane O2 permeability can enhance N2 fixation and growth of Trichodesmium by over 50%. High O2 permeability (1.5 × 10-4 of O2 diffusivity in seawater) during strong photosynthesis accelerates O2 exhaust, reducing energy-consuming photorespiration by ~40%, while low O2 permeability (1.0 × 10-5 diffusivity) during active N2 fixation minimizes O2 stress on N2 fixation. Together, these mechanisms increase the carbon and iron use efficiencies by ~70%. Our study provides a mechanistic and quantitative framework for how dynamic O2 permeability benefits Trichodesmium, offering insights potentially applicable to other diazotrophs.IMPORTANCETrichodesmium is a key player in marine N2 fixation, essential for oceanic productivity and global biogeochemical cycles. However, a significant challenge arises from the concurrent photosynthetic production of O2 during N2 fixation, which can inhibit N2 fixation and cause energy-wasting photorespiration. We develop a physiological model showing that Trichodesmium may dynamically regulate membrane O2 permeability to enhance N2 fixation and growth. The model suggests two mechanisms: elevated O2 permeability during the early daytime of strong photosynthesis accelerates O2 exhaust to the environment, reducing photorespiration, while reduced O2 permeability later limits O2 influx from the environment, lowering wasteful respiration and maintaining a low intracellular O2 level for active N2 fixation. These adaptations improve the efficiency of carbon and iron utilization, thereby facilitating N2 fixation and growth in Trichodesmium. This study sheds light on how Trichodesmium and other N2-fixing microorganisms can optimize their physiological processes in response to environmental challenges.

Centre Algatech Institute of Microbiology of the Czech Academy of Sciences Třeboň Czech Republic

Graduate School of Oceanography University of Rhode Island Narragansett Rhode Island USA

Institute for Advanced Study Shenzhen University Shenzhen China

State Key Laboratory of Marine Environmental Science and College of Ocean and Earth Sciences Xiamen University Xiamen China

Zobrazit více v PubMed

Capone DG, Zehr JP, Paerl HW, Bergman B, Carpenter EJ. 1997. Trichodesmium , a globally significant marine cyanobacterium . Science 276:1221–1229. doi: 10.1126/science.276.5316.1221 DOI

Capone DG, Burns JA, Montoya JP, Subramaniam A, Mahaffey C, Gunderson T, Michaels AF, Carpenter EJ. 2005. Nitrogen fixation by Trichodesmium spp.: an important source of new nitrogen to the tropical and subtropical North Atlantic Ocean . Global Biogeochem Cycles 19. doi: 10.1029/2004GB002331 DOI

Reynolds SE, Mather RL, Wolff GA, Williams RG, Landolfi A, Sanders R, Woodward EMS. 2007. How widespread and important is N DOI

Berman-Frank I, Lundgren P, Chen YB, Küpper H, Kolber Z, Bergman B, Falkowski P. 2001. Segregation of nitrogen fixation and oxygenic photosynthesis in the marine cyanobacterium Trichodesmium. Science 294:1534–1537. doi: 10.1126/science.1064082 PubMed DOI

Staal M, Rabouille S, Stal LJ. 2007. On the role of oxygen for nitrogen fixation in the marine cyanobacterium Trichodesmium sp. Environ Microbiol 9:727–736. doi: 10.1111/j.1462-2920.2006.01195.x PubMed DOI

Wang ZC, Burns A, Watt GD. 1985. Complex formation and O PubMed DOI

Held NA, Waterbury JB, Webb EA, Kellogg RM, McIlvin MR, Jakuba M, Valois FW, Moran DM, Sutherland KM, Saito MA. 2022. Dynamic diel proteome and daytime nitrogenase activity supports buoyancy in the cyanobacterium Trichodesmium. Nat Microbiol 7:300–311. doi: 10.1038/s41564-021-01028-1 PubMed DOI PMC

Hania A, López-Adams R, PrášIl O, Eichner M. 2023. Protection of nitrogenase from photosynthetic O PubMed DOI PMC

Finzi-Hart JA, Pett-Ridge J, Weber PK, Popa R, Fallon SJ, Gunderson T, Hutcheon ID, Nealson KH, Capone DG. 2009. Fixation and fate of C and N in the cyanobacterium Trichodesmium using nanometer-scale secondary ion mass spectrometry. Proc Natl Acad Sci USA 106:6345–6350. doi: 10.1073/pnas.0810547106 PubMed DOI PMC

Luo W, Inomura K, Zhang H, Luo YW. 2022. N2 fixation in Trichodesmium does not require spatial segregation from photosynthesis mSystems 7:e00538–22. doi: 10.1128/msystems.00538-22 PubMed DOI PMC

Nicholson DP, Stanley RHR, Doney SC. 2018. A phytoplankton model for the allocation of gross photosynthetic energy including the trade‐offs of diazotrophy. JGR Biogeosciences 123:1796–1816. doi: 10.1029/2017JG004263 DOI

Inomura K, Wilson ST, Deutsch C. 2019. Mechanistic model for the coexistence of nitrogen fixation and photosynthesis in marine Trichodesmium mSystems 4:e00210-19. doi: 10.1128/mSystems.00210-19 PubMed DOI PMC

Eichner M, Thoms S, Rost B, Mohr W, Ahmerkamp S, Ploug H, Kuypers MMM, de Beer D. 2019. N PubMed DOI PMC

Moroney JV, Jungnick N, DiMario RJ, Longstreth DJ. 2013. Photorespiration and carbon concentrating mechanisms: two adaptations to high O PubMed DOI

Bauwe H, Hagemann M, Fernie AR. 2010. Photorespiration: players, partners and origin. Trends Plant Sci 15:330–336. doi: 10.1016/j.tplants.2010.03.006 PubMed DOI

Li H, Gao K. 2023. Deoxygenation enhances photosynthetic performance and increases N PubMed DOI PMC

Eisenhut M, Roell MS, Weber APM. 2019. Mechanistic understanding of photorespiration paves the way to a new green revolution. New Phytol 223:1762–1769. doi: 10.1111/nph.15872 PubMed DOI

Cornejo-Castillo FM, Zehr JP. 2019. Hopanoid lipids may facilitate aerobic nitrogen fixation in the ocean. Proc Natl Acad Sci USA 116:18269–18271. doi: 10.1073/pnas.1908165116 PubMed DOI PMC

Poger D, Mark AE. 2013. The relative effect of sterols and hopanoids on lipid bilayers: when comparable is not identical. J Phys Chem B 117:16129–16140. doi: 10.1021/jp409748d PubMed DOI

Belin BJ, Busset N, Giraud E, Molinaro A, Silipo A, Newman DK. 2018. Hopanoid lipids: from membranes to plant-bacteria interactions. Nat Rev Microbiol 16:304–315. doi: 10.1038/nrmicro.2017.173 PubMed DOI PMC

Frischkorn KR, Haley ST, Dyhrman ST. 2018. Coordinated gene expression between Trichodesmium and its microbiome over day-night cycles in the North Pacific Subtropical Gyre. ISME J 12:997–1007. doi: 10.1038/s41396-017-0041-5 PubMed DOI PMC

Luo W, Luo YW. 2023. Diurnally dynamic iron allocation promotes N PubMed DOI PMC

Allen JF. 2003. Cyclic, pseudocyclic and noncyclic photophosphorylation: new links in the chain. Trends Plant Sci 8:15–19. doi: 10.1016/s1360-1385(02)00006-7 PubMed DOI

Geider RJ, Moore CM, Ross ON. 2009. The role of cost–benefit analysis in models of phytoplankton growth and acclimation. Plant Ecology & Diversity 2:165–178. doi: 10.1080/17550870903300949 DOI

Milligan AJ, Berman‐Frank I, Gerchman Y, Dismukes GC, Falkowski PG. 2007. Light‐dependent oxygen consumption in nitrogen‐fixing cyanobacteria plays a key role in nitrogenase protection. J Phycol 43:845–852. doi: 10.1111/j.1529-8817.2007.00395.x DOI

Bergman B, Siddiqui PJA, Carpenter EJ, Peschek GA. 1993. Cytochrome oxidase: subcellular distribution and relationship to nitrogenase expression in the nonheterocystous marine cyanobacterium Trichodesmium thiebautii. Appl Environ Microbiol 59:3239–3244. doi: 10.1128/aem.59.10.3239-3244.1993 PubMed DOI PMC

Kana TM. 1993. Rapid oxygen cycling in Trichodesmium thiebautii. Limnology & Oceanography 38:18–24. doi: 10.4319/lo.1993.38.1.0018 DOI

Staal M, Meysman FJR, Stal LJ. 2003. Temperature excludes N PubMed DOI

Benson BB, Krause D. 1984. The concentration and isotopic fractionation of oxygen dissolved in freshwater and seawater in equilibrium with the atmosphere. Limnology & Oceanography 29:620–632. doi: 10.4319/lo.1984.29.3.0620 DOI

Bowes G, Ogren WL, Hageman RH. 1971. Phosphoglycolate production catalyzed by ribulose diphosphate carboxylase. Biochem Biophys Res Commun 45:716–722. doi: 10.1016/0006-291x(71)90475-x PubMed DOI

Flores E, Herrero A. 1994. Assimilatory nitrogen metabolism and its regulation, p 487–517. In Bryant DA (ed), The molecular biology of cyanobacteria. Kluwer Academic Publishers, Dordrecht.

Flores E, Frías JE, Rubio LM, Herrero A. 2005. Photosynthetic nitrate assimilation in cyanobacteria. Photosynth Res 83:117–133. doi: 10.1007/s11120-004-5830-9 PubMed DOI

Luo YW, Shi D, Kranz SA, Hopkinson BM, Hong H, Shen R, Zhang F. 2019. Reduced nitrogenase efficiency dominates response of the globally important nitrogen fixer Trichodesmium to ocean acidification. Nat Commun 10:1521. doi: 10.1038/s41467-019-09554-7 PubMed DOI PMC

Shi D, Kranz SA, Kim JM, Morel FMM. 2012. Ocean acidification slows nitrogen fixation and growth in the dominant diazotroph Trichodesmium under low-iron conditions. Proc Natl Acad Sci USA 109:E3094–100. doi: 10.1073/pnas.1216012109 PubMed DOI PMC

Hong H, Shen R, Zhang F, Wen Z, Chang S, Lin W, Kranz SA, Luo YW, Kao SJ, Morel FMM, Shi D. 2017. The complex effects of ocean acidification on the prominent N PubMed DOI

Gallon JR. 1981. The oxygen sensitivity of nitrogenase: a problem for biochemists and micro-organisms. Trends Biochem Sci 6:19–23. doi: 10.1016/0968-0004(81)90008-6 DOI

Baker NR, Harbinson J, Kramer DM. 2007. Determining the limitations and regulation of photosynthetic energy transduction in leaves. Plant Cell Environ 30:1107–1125. doi: 10.1111/j.1365-3040.2007.01680.x PubMed DOI

Pahlow M, Dietze H, Oschlies A. 2013. Optimality-based model of phytoplankton growth and diazotrophy. Mar Ecol Prog Ser 489:1–16. doi: 10.3354/meps10449 DOI

Leggett RW, Williams LR. 1981. A reliability index for models. Ecol Modell 13:303–312. doi: 10.1016/0304-3800(81)90034-X DOI

Stow CA, Jolliff J, McGillicuddy DJ, Doney SC, Allen JI, Friedrichs MAM, Rose KA, Wallhead P. 2009. Skill assessment for coupled biological/physical models of marine systems. J Mar Syst 76:4–15. doi: 10.1016/j.jmarsys.2008.03.011 PubMed DOI PMC

Reimers AM, Knoop H, Bockmayr A, Steuer R. 2017. Cellular trade-offs and optimal resource allocation during cyanobacterial diurnal growth. Proc Natl Acad Sci USA 114:E6457–E6465. doi: 10.1073/pnas.1617508114 PubMed DOI PMC

Zhang F, Hong H, Kranz SA, Shen R, Lin W, Shi D. 2019. Proteomic responses to ocean acidification of the marine diazotroph Trichodesmium under iron-replete and iron-limited conditions. Photosynth Res 142:17–34. doi: 10.1007/s11120-019-00643-8 PubMed DOI

Jiang HB, Fu FX, Rivero-Calle S, Levine NM, Sañudo-Wilhelmy SA, Qu PP, Wang XW, Pinedo-Gonzalez P, Zhu Z, Hutchins DA. 2018. Ocean warming alleviates iron limitation of marine nitrogen fixation. Nature Clim Change 8:709–712. doi: 10.1038/s41558-018-0216-8 DOI

Kranz SA, Eichner M, Rost B. 2011. Interactions between CCM and N PubMed DOI

Boatman TG, Davey PA, Lawson T, Geider RJ. 2019. CO PubMed DOI PMC

Kana TM. 1992. Oxygen cycling in cyanobacteria, with specific reference to oxygen protection in

Inomura K, Bragg J, Riemann L, Follows MJ. 2018. A quantitative model of nitrogen fixation in the presence of ammonium. PLOS ONE 13:e0208282. doi: 10.1371/journal.pone.0208282 PubMed DOI PMC

Inomura K, Deutsch C, Wilson ST, Masuda T, Lawrenz E, Lenka B, Sobotka R, Gauglitz JM, Saito MA, Prášil O, Follows MJ. 2019. Quantifying oxygen management and temperature and light dependencies of nitrogen fixation by Crocosphaera watsonii. mSphere 4:e00531-19. doi: 10.1128/mSphere.00531-19 PubMed DOI PMC

Großkopf T, Laroche J. 2012. Direct and indirect costs of dinitrogen fixation in Crocosphaera watsonii WH8501 and possible implications for the nitrogen cycle. Front Microbiol 3:236. doi: 10.3389/fmicb.2012.00236 PubMed DOI PMC

Inomura K, Bragg J, Follows MJ. 2017. A quantitative analysis of the direct and indirect costs of nitrogen fixation: a model based on Azotobacter vinelandii. ISME J 11:166–175. doi: 10.1038/ismej.2016.97 PubMed DOI PMC

Wannicke N, Koch BP, Voss M. 2009. Release of fixed N DOI

Cai X, Gao K. 2015. Levels of daily light doses under changed day-night cycles regulate temporal segregation of photosynthesis and N PubMed DOI PMC

Shao Z, Xu Y, Wang H, Luo W, Wang L, Huang Y, Agawin NSR, Ahmed A, Benavides M, Bentzon-Tilia M, et al. 2023. Global oceanic diazotroph database version 2 and elevated estimate of global oceanic N DOI

Olsen A, Lange N, Key RM, Tanhua T, Bittig HC, Kozyr A, Álvarez M, Azetsu-Scott K, Becker S, Brown PJ, et al. 2020. An updated version of the global interior ocean biogeochemical data product, GLODAPv2.2020. Earth Syst Sci Data 12:3653–3678. doi: 10.5194/essd-12-3653-2020 DOI

Eichner MJ, Klawonn I, Wilson ST, Littmann S, Whitehouse MJ, Church MJ, Kuypers MM, Karl DM, Ploug H. 2017. Chemical microenvironments and single-cell carbon and nitrogen uptake in field-collected colonies of Trichodesmium under different pCO PubMed DOI PMC

Muñoz-Marín MDC, Shilova IN, Shi T, Farnelid H, Cabello AM, Zehr JP. 2019. The transcriptional cycle is suited to daytime N2 fixation in the unicellular cyanobacterium “Candidatus Atelocyanobacterium thalassa(UCYN-A). mBio 10:e02495–18. doi: 10.1128/mBio.02495-18 PubMed DOI PMC

Sáenz JP, Waterbury JB, Eglinton TI, Summons RE. 2012. Hopanoids in marine cyanobacteria: probing their phylogenetic distribution and biological role. Geobiology 10:311–319. doi: 10.1111/j.1472-4669.2012.00318.x PubMed DOI

Cornejo-Castillo FM, Cabello AM, Salazar G, Sánchez-Baracaldo P, Lima-Mendez G, Hingamp P, Alberti A, Sunagawa S, Bork P, de Vargas C, Raes J, Bowler C, Wincker P, Zehr JP, Gasol JM, Massana R, Acinas SG. 2016. Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton. Nat Commun 7:11071. doi: 10.1038/ncomms11071 PubMed DOI PMC

Talbot HM, Summons RE, Jahnke LL, Cockell CS, Rohmer M, Farrimond P. 2008. Cyanobacterial bacteriohopanepolyol signatures from cultures and natural environmental settings. Org Geochem 39:232–263. doi: 10.1016/j.orggeochem.2007.08.006 DOI

Coale TH, Loconte V, Turk-Kubo KA, Vanslembrouck B, Mak WKE, Cheung S, Ekman A, Chen JH, Hagino K, Takano Y, Nishimura T, Adachi M, Le Gros M, Larabell C, Zehr JP. 2024. Nitrogen-fixing organelle in a marine alga. Science 384:217–222. doi: 10.1126/science.adk1075 PubMed DOI

Cornejo-Castillo FM, Inomura K, Zehr JP, Follows MJ. 2024. Metabolic trade-offs constrain the cell size ratio in a nitrogen-fixing symbiosis. Cell 187:1762–1768. doi: 10.1016/j.cell.2024.02.016 PubMed DOI

Wilson ST, Aylward FO, Ribalet F, Barone B, Casey JR, Connell PE, Eppley JM, Ferrón S, Fitzsimmons JN, Hayes CT, Romano AE, Turk-Kubo KA, Vislova A, Armbrust EV, Caron DA, Church MJ, Zehr JP, Karl DM, DeLong EF. 2017. Coordinated regulation of growth, activity and transcription in natural populations of the unicellular nitrogen-fixing cyanobacterium Crocosphaera. Nat Microbiol 2. doi: 10.1038/nmicrobiol.2017.118 PubMed DOI

Cheah YE, Zimont AJ, Lunka SK, Albers SC, Park SJ, Reardon KF, Peebles CAM. 2015. Diel light:dark cycles significantly reduce FFA accumulation in FFA producing mutants of Synechocystis sp. PCC 6803 compared to continuous light. Algal Res 12:487–496. doi: 10.1016/j.algal.2015.10.014 DOI

Munnik T, Mongrand S, Zársky V, Blatt M. 2021. Dynamic membranes-the indispensable platform for plant growth, signaling, and development. Plant Physiol 185:547–549. doi: 10.1093/plphys/kiaa107 PubMed DOI PMC

Zehr JP. 2011. Nitrogen fixation by marine cyanobacteria. Trends Microbiol 19:162–173. doi: 10.1016/j.tim.2010.12.004 PubMed DOI

Berman-Frank I, Lundgren P, Falkowski P. 2003. Nitrogen fixation and photosynthetic oxygen evolution in cyanobacteria. Res Microbiol 154:157–164. doi: 10.1016/S0923-2508(03)00029-9 PubMed DOI

Zehr JP, Capone DG. 2020. Changing perspectives in marine nitrogen fixation. Science 368:eaay9514. doi: 10.1126/science.aay9514 PubMed DOI

Gao M, Andrews J, Armin G, Chakraborty S, Zehr JP, Inomura K. 2024. Rapid mode switching facilitates the growth of Trichodesmium: a model analysis. iScience 27:109906. doi: 10.1016/j.isci.2024.109906 PubMed DOI PMC

Tripp HJ, Bench SR, Turk KA, Foster RA, Desany BA, Niazi F, Affourtit JP, Zehr JP. 2010. Metabolic streamlining in an open-ocean nitrogen-fixing cyanobacterium. Nature 464:90–94. doi: 10.1038/nature08786 PubMed DOI

Welsh EA, Liberton M, Stöckel J, Loh T, Elvitigala T, Wang C, Wollam A, Fulton RS, Clifton SW, Jacobs JM, Aurora R, Ghosh BK, Sherman LA, Smith RD, Wilson RK, Pakrasi HB. 2008. The genome of Cyanothece 51142, a unicellular diazotrophic cyanobacterium important in the marine nitrogen cycle. Proc Natl Acad Sci USA 105:15094–15099. doi: 10.1073/pnas.0805418105 PubMed DOI PMC

Saito MA, Bertrand EM, Dutkiewicz S, Bulygin VV, Moran DM, Monteiro FM, Follows MJ, Valois FW, Waterbury JB. 2011. Iron conservation by reduction of metalloenzyme inventories in the marine diazotroph Crocosphaera watsonii . Proc Natl Acad Sci USA 108:2184–2189. doi: 10.1073/pnas.1006943108 PubMed DOI PMC

Masuda T, Inomura K, Mareš J, Prášil O. 2022. Crocosphaera watsonii. Trends Microbiol 30:805–806. doi: 10.1016/j.tim.2022.02.006 PubMed DOI

Masuda T, Inomura K, Takahata N, Shiozaki T, Sano Y, Deutsch C, Prášil O, Furuya K. 2020. Heterogeneous nitrogen fixation rates confer energetic advantage and expanded ecological niche of unicellular diazotroph populations. Commun Biol 3:172. doi: 10.1038/s42003-020-0894-4 PubMed DOI PMC

Sáenz JP. 2010. Hopanoid enrichment in a detergent resistant membrane fraction of Crocosphaera watsonii: Implications for bacterial lipid raft formation. Org Geochem 41:853–856. doi: 10.1016/j.orggeochem.2010.05.005 DOI

Schouten S, Villareal TA, Hopmans EC, Mets A, Swanson KM, Sinninghe Damsté JS. 2013. Endosymbiotic heterocystous cyanobacteria synthesize different heterocyst glycolipids than free-living heterocystous cyanobacteria. Phytochemistry 85:115–121. doi: 10.1016/j.phytochem.2012.09.002 PubMed DOI

Garg R, Maldener I. 2021. The dual role of the glycolipid envelope in different cell types of the multicellular cyanobacterium Anabaena variabilis ATCC 29413. Front Microbiol 12:645028. doi: 10.3389/fmicb.2021.645028 PubMed DOI PMC

Berman-Frank I, Quigg A, Finkel ZV, Irwin AJ, Haramaty L. 2007. Nitrogen‐fixation strategies and Fe requirements in cyanobacteria. Limnology & Oceanography 52:2260–2269. doi: 10.4319/lo.2007.52.5.2260 DOI