{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T05:24:34Z","timestamp":1781241874180,"version":"3.54.1"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Helmholtz-Zentrum f\u00fcr Umweltforschung GmbH - UFZ"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microb Cell Fact"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In response to rising CO\n                      <jats:sub>2<\/jats:sub>\n                      emissions driving global warming, there is an urgent need for a transition toward a sustainable bioeconomy. Photo-biotechnological processes based on oxygenic photosynthesis hold high potential for achieving CO\n                      <jats:sub>2<\/jats:sub>\n                      neutrality and in this regard, cyanobacteria have emerged as promising biocatalysts. Rational metabolic engineering of cyanobacteria depends on a thorough understanding of regulatory mechanisms governing primary metabolism, because native metabolic flux through specific pathways and, consequently, the formation of target products can be limited. Recent insights have identified a key regulatory node at the 2,3-bisphosphogylcerate-independent phosphoglycerate mutase (PGAM) reaction, where the metabolic flux from newly fixed carbon is redirected from the Calvin-Benson-Bassham (CBB) cycle towards lower glycolysis. This metabolic valve is controlled by the small inhibitor protein PirC, whose binding to PGAM is determined by the central signal transduction protein PII.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, we exploit the PirC-PGAM interaction as a novel target for regulatory metabolic engineering in the model cyanobacterium\n                      <jats:italic>Synechocystis<\/jats:italic>\n                      sp. PCC 6803 (\n                      <jats:italic>Synechocystis<\/jats:italic>\n                      ). Chassis strains with engineered control of PGAM, defined as PGAM-ON or PGAM-OFF states, were generated using two complementary approaches: tuning\n                      <jats:italic>pgam<\/jats:italic>\n                      gene expression and modulating PirC abundance to regulate PGAM activity. The effectiveness of this regulatory engineering strategy was demonstrated by redirecting carbon flux toward two representative, naturally occurring products: sucrose, produced via gluconeogenesis fueled by the Calvin-Benson-Bassham (CBB) cycle, and succinate, an intermediate of the tricarboxylic acid (TCA) cycle. Narrowing the PGAM valve resulted in a threefold increase in sucrose accumulation. In contrast, opening the PGAM valve by relieving PGAM inhibition through\n                      <jats:italic>pirC<\/jats:italic>\n                      deletion or separate\n                      <jats:italic>pgam<\/jats:italic>\n                      overexpression resulted in up to an 18-fold increase in succinate excretion. Furthermore, similar genetic configurations were applied to enhance production of a heterologous compound, isoprene, derived from pyruvate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study establishes the PGAM valve as a tunable control point for the rational re-direction of carbon flux in\n                      <jats:italic>Synechocystis<\/jats:italic>\n                      and highlights small regulatory proteins as powerful targets for metabolic engineering. Together, these findings provide proof of concept for an advanced level of molecular engineering in cyanobacteria and to fully harness their biocatalytic potential in future photosynthesis-driven biotechnological applications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12934-026-03033-7","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T07:34:21Z","timestamp":1779262461000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Conversion of CO2 into valuable products: engineering the PirC-PGAM switch in cyanobacteria to direct carbon flux into desired products"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6893-1181","authenticated-orcid":false,"given":"Nathalie Sofie","family":"Becker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Hufnagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bolay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Otec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Orthwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kulik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipp","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius","family":"Lenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Forchhammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-486X","authenticated-orcid":false,"given":"Stephan","family":"Kl\u00e4hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"3033_CR1","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1146\/annurev-arplant-042110-103811","volume":"62","author":"MF Hohmann-Marriott","year":"2011","unstructured":"Hohmann-Marriott MF, Blankenship RE. Evolution of photosynthesis. Annu Rev Plant Biol. 2011;62:515\u201348. https:\/\/doi.org\/10.1146\/annurev-arplant-042110-103811.","journal-title":"Annu Rev Plant Biol"},{"key":"3033_CR2","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1126\/science.1153213","volume":"320","author":"PG Falkowski","year":"2008","unstructured":"Falkowski PG, Fenchel T, Delong EF. The microbial engines that drive Earth\u2019s biogeochemical cycles. Science. 2008;320:1034\u20139. https:\/\/doi.org\/10.1126\/science.1153213.","journal-title":"Science"},{"key":"3033_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.tibtech.2010.12.003","volume":"29","author":"DC Ducat","year":"2011","unstructured":"Ducat DC, Way JC, Silver PA. Engineering cyanobacteria to generate high-value products. Trends Biotechnol. 2011;29:95\u2013103. https:\/\/doi.org\/10.1016\/j.tibtech.2010.12.003.","journal-title":"Trends Biotechnol"},{"key":"3033_CR4","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.tibtech.2015.03.009","volume":"33","author":"SA Angermayr","year":"2015","unstructured":"Angermayr SA, Gorchs Rovira A, Hellingwerf KJ. Metabolic engineering of cyanobacteria for the synthesis of commodity products. Trends Biotechnol. 2015;33:352\u201361. https:\/\/doi.org\/10.1016\/j.tibtech.2015.03.009.","journal-title":"Trends Biotechnol"},{"key":"3033_CR5","doi-asserted-by":"publisher","first-page":"102892","DOI":"10.1016\/j.copbio.2023.102892","volume":"80","author":"J Toepel","year":"2023","unstructured":"Toepel J, Karande R, Kl\u00e4hn S, B\u00fchler B. Cyanobacteria as whole-cell factories: current status and future prospectives. Curr Opin Biotechnol. 2023;80:102892. https:\/\/doi.org\/10.1016\/j.copbio.2023.102892.","journal-title":"Curr Opin Biotechnol"},{"key":"3033_CR6","doi-asserted-by":"publisher","first-page":"e14316","DOI":"10.1111\/ppl.14316","volume":"176","author":"P Bolay","year":"2024","unstructured":"Bolay P, Dodge N, Janssen K, Jensen PE, Lindberg P. Tailoring regulatory components for metabolic engineering in cyanobacteria. Physiol Plant. 2024;176:e14316. https:\/\/doi.org\/10.1111\/ppl.14316.","journal-title":"Physiol Plant"},{"key":"3033_CR7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.greenca.2024.05.002","volume":"2","author":"S Kl\u00e4hn","year":"2024","unstructured":"Kl\u00e4hn S, Opel F, Hess WR. Customized molecular tools to strengthen metabolic engineering of cyanobacteria. Green Carbon. 2024;2:149\u201363. https:\/\/doi.org\/10.1016\/j.greenca.2024.05.002.","journal-title":"Green Carbon"},{"key":"3033_CR8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/femsre\/fuz025","volume":"44","author":"K Forchhammer","year":"2020","unstructured":"Forchhammer K, Selim KA. Carbon\/nitrogen homeostasis control in cyanobacteria. FEMS Microbiol Rev. 2020;44:33\u201353. https:\/\/doi.org\/10.1093\/femsre\/fuz025.","journal-title":"FEMS Microbiol Rev"},{"key":"3033_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2021.12.014","author":"K Forchhammer","year":"2022","unstructured":"Forchhammer K, Selim KA, Huergo LF. New views on PII signaling: from nitrogen sensing to global metabolic control. Trends Microbiol. 2022. https:\/\/doi.org\/10.1016\/j.tim.2021.12.014.","journal-title":"Trends Microbiol"},{"key":"3033_CR10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1128\/MMBR.00038-15","volume":"79","author":"LF Huergo","year":"2015","unstructured":"Huergo LF, Dixon R. The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite. Microbiol Mol Biol Rev. 2015;79:419\u201335. https:\/\/doi.org\/10.1128\/MMBR.00038-15.","journal-title":"Microbiol Mol Biol Rev"},{"key":"3033_CR11","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/febs.13584","volume":"283","author":"K Forchhammer","year":"2016","unstructured":"Forchhammer K, L\u00fcddecke J. Sensory properties of the PII signalling protein family. FEBS J. 2016;283:425\u201337. https:\/\/doi.org\/10.1111\/febs.13584.","journal-title":"FEBS J"},{"key":"3033_CR12","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/j.1365-2958.2006.05231.x","volume":"61","author":"J Espinosa","year":"2006","unstructured":"Espinosa J, Forchhammer K, Burillo S, Contreras A. Interaction network in cyanobacterial nitrogen regulation: PipX, a protein that interacts in a 2-oxoglutarate dependent manner with PII and NtcA. Mol Microbiol. 2006;61:457\u201369. https:\/\/doi.org\/10.1111\/j.1365-2958.2006.05231.x.","journal-title":"Mol Microbiol"},{"key":"3033_CR13","doi-asserted-by":"publisher","first-page":"E2423","DOI":"10.1073\/pnas.1404097111","volume":"111","author":"J Espinosa","year":"2014","unstructured":"Espinosa J, Rodr\u00edguez-Mateos F, Salinas P, Lanza VF, Dixon R, de la Cruz F, et al. PipX, the coactivator of NtcA, is a global regulator in cyanobacteria. Proc Natl Acad Sci USA. 2014;111:E2423\u20132430. https:\/\/doi.org\/10.1073\/pnas.1404097111.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3033_CR14","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1111\/j.1365-2958.2004.04058.x","volume":"52","author":"A Heinrich","year":"2004","unstructured":"Heinrich A, Maheswaran M, Ruppert U, Forchhammer K. The Synechococcus elongatus P signal transduction protein controls arginine synthesis by complex formation with N-acetyl-L-glutamate kinase. Mol Microbiol. 2004;52:1303\u201314. https:\/\/doi.org\/10.1111\/j.1365-2958.2004.04058.x.","journal-title":"Mol Microbiol"},{"key":"3033_CR15","doi-asserted-by":"publisher","first-page":"55202","DOI":"10.1074\/jbc.M410971200","volume":"279","author":"M Maheswaran","year":"2004","unstructured":"Maheswaran M, Urbanke C, Forchhammer K. Complex Formation and Catalytic Activation by the PII Signaling Protein of N-Acetyl-l-glutamate Kinase from Synechococcus elongatus Strain PCC 7942. J Biol Chem. 2004;279:55202\u201310. https:\/\/doi.org\/10.1074\/jbc.M410971200.","journal-title":"J Biol Chem"},{"key":"3033_CR16","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.3389\/fmicb.2016.01700","volume":"7","author":"W Hauf","year":"2016","unstructured":"Hauf W, Schmid K, Gerhardt ECM, Huergo LF, Forchhammer K. Interaction of the nitrogen regulatory protein GlnB (PII) with biotin carboxyl carrier protein (BCCP) controls acetyl-CoA levels in the cyanobacterium Synechocystis sp. PCC 6803. Front Microbiol. 2016;7:1700. https:\/\/doi.org\/10.3389\/fmicb.2016.01700.","journal-title":"Front Microbiol"},{"key":"3033_CR17","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15845","author":"R Steinberg","year":"2021","unstructured":"Steinberg R, Koch H-G. The largely unexplored biology of small proteins in pro- and eukaryotes. FEBS J. 2021. https:\/\/doi.org\/10.1111\/febs.15845.","journal-title":"FEBS J"},{"key":"3033_CR18","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s12866-016-0896-z","volume":"16","author":"D Baumgartner","year":"2016","unstructured":"Baumgartner D, Kopf M, Kl\u00e4hn S, Steglich C, Hess WR. Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome. BMC Microbiol. 2016;16:285. https:\/\/doi.org\/10.1186\/s12866-016-0896-z.","journal-title":"BMC Microbiol"},{"key":"3033_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/life10120322","author":"F Brandenburg","year":"2020","unstructured":"Brandenburg F, Kl\u00e4hn S. Small but smart: on the diverse role of small proteins in the regulation of cyanobacterial metabolism. Life (Basel). 2020. https:\/\/doi.org\/10.3390\/life10120322.","journal-title":"Life (Basel)"},{"key":"3033_CR20","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1099\/mic.0.2006\/003574-0","volume":"153","author":"J Espinosa","year":"2007","unstructured":"Espinosa J, Forchhammer K, Contreras A. Role of the Synechococcus PCC 7942 nitrogen regulator protein PipX in NtcA-controlled processes. Microbiol (Reading). 2007;153:711\u20138. https:\/\/doi.org\/10.1099\/mic.0.2006\/003574-0.","journal-title":"Microbiol (Reading)"},{"key":"3033_CR21","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00229-21","author":"P Bolay","year":"2021","unstructured":"Bolay P, Rozbeh R, Muro-Pastor MI, Timm S, Hagemann M, Florencio FJ, et al. The novel PII-interacting protein PirA controls flux into the cyanobacterial ornithine-ammonia cycle. mBio. 2021. https:\/\/doi.org\/10.1128\/mBio.00229-21.","journal-title":"mBio"},{"key":"3033_CR22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2019988118","author":"T Orthwein","year":"2021","unstructured":"Orthwein T, Scholl J, Sp\u00e4t P, Lucius S, Koch M, Macek B, et al. The novel PII-interactor PirC identifies phosphoglycerate mutase as key control point of carbon storage metabolism in cyanobacteria. Proc Natl Acad Sci U S A. 2021. https:\/\/doi.org\/10.1073\/pnas.2019988118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3033_CR23","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1104\/pp.20.00802","volume":"184","author":"MI Muro-Pastor","year":"2020","unstructured":"Muro-Pastor MI, Cutillas-Farray \u00c1, P\u00e9rez-Rodr\u00edguez L, P\u00e9rez-Saavedra J, Vega-de Armas A, Paredes A, et al. CfrA, a Novel Carbon Flow Regulator, Adapts Carbon Metabolism to Nitrogen Deficiency in Cyanobacteria. Plant Physiol. 2020;184:1792\u2013810. https:\/\/doi.org\/10.1104\/pp.20.00802.","journal-title":"Plant Physiol"},{"key":"3033_CR24","doi-asserted-by":"publisher","first-page":"e03378","DOI":"10.1128\/mbio.03378-24","volume":"16","author":"T Orthwein","year":"2025","unstructured":"Orthwein T, Alford JT, Becker NS, Fink P, Forchhammer K. Structural elements of cyanobacterial co-factor-independent phosphoglycerate mutase that mediate regulation by PirC. mBio. 2025;16:e03378\u201324. https:\/\/doi.org\/10.1128\/mbio.03378-24.","journal-title":"mBio"},{"key":"3033_CR25","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1111\/febs.17348","volume":"292","author":"K Lee","year":"2025","unstructured":"Lee K, Doello S, Hagemann M, Forchhammer K. Deciphering the tight metabolite-level regulation of glucose-1-phosphate adenylyltransferase (GlgC) for glycogen synthesis in cyanobacteria. FEBS J. 2025;292:759\u201375. https:\/\/doi.org\/10.1111\/febs.17348.","journal-title":"FEBS J"},{"key":"3033_CR26","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1186\/s12934-015-0384-4","volume":"14","author":"B Watzer","year":"2015","unstructured":"Watzer B, Engelbrecht A, Hauf W, Stahl M, Maldener I, Forchhammer K. Metabolic pathway engineering using the central signal processor PII. Microb Cell Fact. 2015;14:192. https:\/\/doi.org\/10.1186\/s12934-015-0384-4.","journal-title":"Microb Cell Fact"},{"key":"3033_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1099\/00221287-111-1-1","volume":"111","author":"R Rippka","year":"1979","unstructured":"Rippka R, Deruelles J, Waterbury JB, Herdman M, Stanier RY. Generic assignments, strain histories and properties of pure cultures of cyanobacteria. J Gen Microbiol. 1979;111:1\u201361. https:\/\/doi.org\/10.1099\/00221287-111-1-1.","journal-title":"J Gen Microbiol"},{"key":"3033_CR28","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nmeth.1318","volume":"6","author":"DG Gibson","year":"2009","unstructured":"Gibson DG, Young L, Chuang R-Y, Venter JC, Hutchison CA, Smith HO. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods. 2009;6:343\u20135. https:\/\/doi.org\/10.1038\/nmeth.1318.","journal-title":"Nat Methods"},{"key":"3033_CR29","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s00253-008-1356-y","volume":"78","author":"A Ludwig","year":"2008","unstructured":"Ludwig A, Heimbucher T, Gregor W, Czerny T, Schmetterer G. Transformation and gene replacement in the facultatively chemoheterotrophic, unicellular cyanobacterium Synechocystis sp. PCC6714 by electroporation. Appl Microbiol Biotechnol. 2008;78:729\u201335. https:\/\/doi.org\/10.1007\/s00253-008-1356-y.","journal-title":"Appl Microbiol Biotechnol"},{"key":"3033_CR30","doi-asserted-by":"publisher","first-page":"e0137652","DOI":"10.1371\/journal.pone.0137652","volume":"10","author":"HM Beyer","year":"2015","unstructured":"Beyer HM, Gonschorek P, Samodelov SL, Meier M, Weber W, Zurbriggen MD. AQUA Cloning: A versatile and simple enzyme-free cloning approach. PLoS ONE. 2015;10:e0137652. https:\/\/doi.org\/10.1371\/journal.pone.0137652.","journal-title":"PLoS ONE"},{"key":"3033_CR31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/nprot.2006.4","volume":"1","author":"H Sch\u00e4gger","year":"2006","unstructured":"Sch\u00e4gger H, Tricine- SDS-PAGE. Nat Protoc. 2006;1:16\u201322. https:\/\/doi.org\/10.1038\/nprot.2006.4.","journal-title":"Nat Protoc"},{"key":"3033_CR32","doi-asserted-by":"publisher","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","volume":"76","author":"H Towbin","year":"1979","unstructured":"Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979;76:4350\u20134. https:\/\/doi.org\/10.1073\/pnas.76.9.4350.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3033_CR33","doi-asserted-by":"publisher","first-page":"2767","DOI":"10.3390\/microorganisms13122767","volume":"13","author":"JT Alford","year":"2025","unstructured":"Alford JT, Becker NS, Rapp J, Kulik A, Kaewbai-Ngam J, Monshupanee T, et al. Controlled carbon loss: Threshold-dependent overflow metabolism in Synechocystis sp. PCC 6803. Microorganisms. 2025;13:2767. https:\/\/doi.org\/10.3390\/microorganisms13122767.","journal-title":"Microorganisms"},{"key":"3033_CR34","doi-asserted-by":"publisher","first-page":"3032","DOI":"10.1099\/mic.0.062950-0","volume":"158","author":"M Gr\u00fcndel","year":"2012","unstructured":"Gr\u00fcndel M, Scheunemann R, Lockau W, Zilliges Y. Impaired glycogen synthesis causes metabolic overflow reactions and affects stress responses in the cyanobacterium Synechocystis sp. PCC 6803. Microbiol (Reading). 2012;158:3032\u201343. https:\/\/doi.org\/10.1099\/mic.0.062950-0.","journal-title":"Microbiol (Reading)"},{"key":"3033_CR35","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12934-025-02650-y","volume":"24","author":"P Fink","year":"2025","unstructured":"Fink P, Menzel C, Kwon J-H, Forchhammer K. A novel recombinant PHB production platform in filamentous cyanobacteria avoiding nitrogen starvation while preserving cell viability. Microb Cell Fact. 2025;24:43. https:\/\/doi.org\/10.1186\/s12934-025-02650-y.","journal-title":"Microb Cell Fact"},{"key":"3033_CR36","doi-asserted-by":"publisher","first-page":"5055","DOI":"10.1002\/jsfa.11204","volume":"102","author":"A Hoehnel","year":"2022","unstructured":"Hoehnel A, Salas Garc\u00eda J, Coffey C, Zannini E, Arendt EK. Comparative study of sugar extraction procedures for HPLC analysis and proposal of an ethanolic extraction method for plant-based high-protein ingredients. J Sci Food Agric. 2022;102:5055\u201364. https:\/\/doi.org\/10.1002\/jsfa.11204.","journal-title":"J Sci Food Agric"},{"key":"3033_CR37","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1104\/pp.18.01401","volume":"180","author":"R Vasudevan","year":"2019","unstructured":"Vasudevan R, Gale GAR, Schiavon AA, Puzorjov A, Malin J, Gillespie MD, et al. CyanoGate: A Modular Cloning Suite for Engineering Cyanobacteria Based on the Plant MoClo Syntax. Plant Physiol. 2019;180:39\u201355. https:\/\/doi.org\/10.1104\/pp.18.01401.","journal-title":"Plant Physiol"},{"key":"3033_CR38","doi-asserted-by":"publisher","first-page":"e2519335122","DOI":"10.1073\/pnas.2519335122","volume":"122","author":"MA Itzenh\u00e4user","year":"2025","unstructured":"Itzenh\u00e4user MA, Enkerlin AM, Dewald JA, Av\u015far B, Stauder R, Halpick H, et al. Deciphering guanidine assimilation and riboswitch-based gene regulation in cyanobacteria for synthetic biology applications. Proc Natl Acad Sci U S A. 2025;122:e2519335122. https:\/\/doi.org\/10.1073\/pnas.2519335122.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3033_CR39","doi-asserted-by":"publisher","first-page":"2862","DOI":"10.1016\/j.cub.2016.08.054","volume":"26","author":"A Klotz","year":"2016","unstructured":"Klotz A, Georg J, Bu\u010dinsk\u00e1 L, Watanabe S, Reimann V, Januszewski W, et al. Awakening of a dormant cyanobacterium from nitrogen chlorosis reveals a genetically determined program. Curr Biol. 2016;26:2862\u201372. https:\/\/doi.org\/10.1016\/j.cub.2016.08.054.","journal-title":"Curr Biol"},{"key":"3033_CR40","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1074\/mcp.RA118.000699","volume":"17","author":"P Sp\u00e4t","year":"2018","unstructured":"Sp\u00e4t P, Klotz A, Rexroth S, Ma\u010dek B, Forchhammer K. Chlorosis as a developmental program in cyanobacteria: The proteomic fundament for survival and awakening. Mol Cell Proteom. 2018;17:1650\u201369. https:\/\/doi.org\/10.1074\/mcp.RA118.000699.","journal-title":"Mol Cell Proteom"},{"key":"3033_CR41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017898118","author":"R Garc\u00eda-Ca\u00f1as","year":"2021","unstructured":"Garc\u00eda-Ca\u00f1as R, Giner-Lamia J, Florencio FJ, L\u00f3pez-Maury L. A protease-mediated mechanism regulates the cytochrome c6\/plastocyanin switch in Synechocystis sp. PCC 6803. Proc Natl Acad Sci U S A. 2021. https:\/\/doi.org\/10.1073\/pnas.2017898118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3033_CR42","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jbiotec.2016.09.016","volume":"239","author":"K Namakoshi","year":"2016","unstructured":"Namakoshi K, Nakajima T, Yoshikawa K, Toya Y, Shimizu H. Combinatorial deletions of glgC and phaCE enhance ethanol production in Synechocystis sp. PCC 6803. J Biotechnol. 2016;239:13\u20139. https:\/\/doi.org\/10.1016\/j.jbiotec.2016.09.016.","journal-title":"J Biotechnol"},{"key":"3033_CR43","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s42003-024-05929-9","volume":"7","author":"Y Kato","year":"2024","unstructured":"Kato Y, Hidese R, Matsuda M, Ohbayashi R, Ashida H, Kondo A, et al. Glycogen deficiency enhances carbon partitioning into glutamate for an alternative extracellular metabolic sink in cyanobacteria. Commun Biol. 2024;7:233. https:\/\/doi.org\/10.1038\/s42003-024-05929-9.","journal-title":"Commun Biol"},{"key":"3033_CR44","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1002\/ceat.200800063","volume":"31","author":"I Bechthold","year":"2008","unstructured":"Bechthold I, Bretz K, Kabasci S, Kopitzky R, Springer A. Succinic Acid: A New Platform Chemical for Biobased Polymers from Renewable Resources. Chem Eng Technol. 2008;31:647\u201354. https:\/\/doi.org\/10.1002\/ceat.200800063.","journal-title":"Chem Eng Technol"},{"key":"3033_CR45","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ymben.2009.10.001","volume":"12","author":"P Lindberg","year":"2010","unstructured":"Lindberg P, Park S, Melis A. Engineering a platform for photosynthetic isoprene production in cyanobacteria, using Synechocystis as the model organism. Metab Eng. 2010;12:70\u20139. https:\/\/doi.org\/10.1016\/j.ymben.2009.10.001.","journal-title":"Metab Eng"},{"key":"3033_CR46","doi-asserted-by":"publisher","first-page":"9602","DOI":"10.1039\/D2GC03272D","volume":"24","author":"A Rana","year":"2022","unstructured":"Rana A, Gomes LC, Rodrigues JS, Yacout DMM, Arrou-Vignod H, Sj\u00f6lander J, et al. A combined photobiological\u2013photochemical route to C10 cycloalkane jet fuels from carbon dioxide via isoprene. Green Chem Royal Soc Chem. 2022;24:9602\u201319. https:\/\/doi.org\/10.1039\/D2GC03272D.","journal-title":"Green Chem Royal Soc Chem"},{"key":"3033_CR47","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/j.1462-2920.2010.02366.x","volume":"13","author":"S Kl\u00e4hn","year":"2011","unstructured":"Kl\u00e4hn S, Hagemann M. Compatible solute biosynthesis in cyanobacteria. Environ Microbiol. 2011;13:551\u201362. https:\/\/doi.org\/10.1111\/j.1462-2920.2010.02366.x.","journal-title":"Environ Microbiol"},{"key":"3033_CR48","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02139","author":"F Kirsch","year":"2019","unstructured":"Kirsch F, Kl\u00e4hn S, Hagemann M. Salt-regulated accumulation of the compatible solutes sucrose and glucosylglycerol in cyanobacteria and its biotechnological potential. Front Microbiol [Internet]. 2019. https:\/\/doi.org\/10.3389\/fmicb.2019.02139. [cited 2021 Mar 22];10.","journal-title":"Front Microbiol [Internet]"},{"key":"3033_CR49","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/s12934-020-01491-1","volume":"19","author":"M Koch","year":"2020","unstructured":"Koch M, Bruckmoser J, Scholl J, Hauf W, Rieger B, Forchhammer K. Maximizing PHB content in Synechocystis sp. PCC 6803: a new metabolic engineering strategy based on the regulator PirC. Microb Cell Fact. 2020;19:231. https:\/\/doi.org\/10.1186\/s12934-020-01491-1.","journal-title":"Microb Cell Fact"},{"key":"3033_CR50","doi-asserted-by":"publisher","first-page":"1238737","DOI":"10.3389\/fmicb.2023.1238737","volume":"14","author":"J B\u00f6hm","year":"2023","unstructured":"B\u00f6hm J, Kauss K, Michl K, Engelhardt L, Brouwer E-M, Hagemann M. Impact of the carbon flux regulator protein pirC on ethanol production in engineered cyanobacteria. Front Microbiol. 2023;14:1238737. https:\/\/doi.org\/10.3389\/fmicb.2023.1238737.","journal-title":"Front Microbiol"},{"key":"3033_CR51","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1093\/plphys\/kiae083","volume":"195","author":"MT Dom\u00ednguez-Lobo","year":"2024","unstructured":"Dom\u00ednguez-Lobo MT, Rold\u00e1n M, Guti\u00e9rrez-Di\u00e1nez AM, Florencio FJ, Muro-Pastor MI. Double blocking of carbon metabolism causes a large increase of Calvin-Benson cycle compounds in cyanobacteria. Plant Physiol. 2024;195:1491\u2013505. https:\/\/doi.org\/10.1093\/plphys\/kiae083.","journal-title":"Plant Physiol"},{"key":"3033_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-025-02894-8","author":"MT Dom\u00ednguez-Lobo","year":"2025","unstructured":"Dom\u00ednguez-Lobo MT, Ortega-Mart\u00ednez P, Florencio FJ, Muro-Pastor MI. Enhanced sucrose production by controlling carbon flux through CfrA expression in Synechocystis sp. PCC 6803. Microb Cell Fact. 2025. https:\/\/doi.org\/10.1186\/s12934-025-02894-8.","journal-title":"Microb Cell Fact"},{"key":"3033_CR53","doi-asserted-by":"publisher","first-page":"101645","DOI":"10.1016\/j.algal.2019.101645","volume":"43","author":"M Mock","year":"2019","unstructured":"Mock M, Schmid A, B\u00fchler K. Photoautotrophic production of succinate via the oxidative branch of the tricarboxylic acid cycle influences glycogen accumulation in Synechocystis sp. PCC 6803. Algal Res. 2019;43:101645. https:\/\/doi.org\/10.1016\/j.algal.2019.101645.","journal-title":"Algal Res"},{"key":"3033_CR54","doi-asserted-by":"publisher","first-page":"e2000127","DOI":"10.1002\/biot.202000127","volume":"15","author":"M Mock","year":"2020","unstructured":"Mock M, Schmid A, B\u00fchler K. Directed reaction engineering boosts succinate formation of Synechocystis sp. PCC 6803_\u2206sll1625. Biotechnol J. 2020;15:e2000127. https:\/\/doi.org\/10.1002\/biot.202000127.","journal-title":"Biotechnol J"},{"key":"3033_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-021-01529-y","author":"C Durall","year":"2021","unstructured":"Durall C, Kukil K, Hawkes JA, Albergati A, Lindblad P, Lindberg P. Production of succinate by engineered strains of Synechocystis PCC 6803 overexpressing phosphoenolpyruvate carboxylase and a glyoxylate shunt. Microb Cell Fact [Internet]. 2021. https:\/\/doi.org\/10.1186\/s12934-021-01529-y. [cited 2021 Mar 22];20.","journal-title":"Microb Cell Fact [Internet]"},{"key":"3033_CR56","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ymben.2013.05.001","volume":"19","author":"W Du","year":"2013","unstructured":"Du W, Liang F, Duan Y, Tan X, Lu X. Exploring the photosynthetic production capacity of sucrose by cyanobacteria. Metab Eng. 2013;19:17\u201325. https:\/\/doi.org\/10.1016\/j.ymben.2013.05.001.","journal-title":"Metab Eng"},{"key":"3033_CR57","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1099\/mic.0.000708","volume":"164","author":"F Kirsch","year":"2018","unstructured":"Kirsch F, Luo Q, Lu X, Hagemann M. Inactivation of invertase enhances sucrose production in the cyanobacterium Synechocystis sp. PCC 6803. Microbiol (Reading). 2018;164:1220\u20138. https:\/\/doi.org\/10.1099\/mic.0.000708.","journal-title":"Microbiol (Reading)"},{"key":"3033_CR58","doi-asserted-by":"publisher","first-page":"100236","DOI":"10.1016\/j.biteb.2019.100236","volume":"7","author":"GA Colusse","year":"2019","unstructured":"Colusse GA, Duarte MER, de Carvalho JC, Noseda MD. Media effects on laboratory scale production costs of Haematococcus pluvialis biomass. Bioresource Technol Rep. 2019;7:100236. https:\/\/doi.org\/10.1016\/j.biteb.2019.100236.","journal-title":"Bioresource Technol Rep"},{"key":"3033_CR59","doi-asserted-by":"publisher","first-page":"103064","DOI":"10.1016\/j.algal.2023.103064","volume":"71","author":"S Canizales","year":"2023","unstructured":"Canizales S, Chen P-H, Temmink H, Wijffels RH, Janssen M. Cyanobacteria cultivation on human urine for nutrients recovery. Algal Res. 2023;71:103064. https:\/\/doi.org\/10.1016\/j.algal.2023.103064.","journal-title":"Algal Res"}],"container-title":["Microbial Cell Factories"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12934-026-03033-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-026-03033-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-026-03033-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:58:07Z","timestamp":1779346687000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12934-026-03033-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3033"],"URL":"https:\/\/doi.org\/10.1186\/s12934-026-03033-7","relation":{},"ISSN":["1475-2859"],"issn-type":[{"value":"1475-2859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"6 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S.K. is an associate editor of the journal Microbial Cell Factories. The peer-review of this paper was therefore overseen by an independent member of the editorial board while the submission was subject to the exact same review process as applied to any other manuscript. Beyond that the authors declare no further competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"128"}}