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These organisms function as green cell factories capable of directly converting carbon dioxide into organic carbon metabolites using solar energy, offering a promising platform for more sustainable biomanufacturing. Among these organisms, cyanobacteria, and particularly Synechocystis sp. PCC 6803, have emerged as particularly attractive hosts due to their relatively simple cellular organization, efficient photosynthetic metabolism, and amenability to genetic manipulation. In addition to rational metabolic engineering approaches, Adaptive Laboratory Evolution (ALE) has recently been proposed as a powerful strategy to improve Synechocystis strain robustness, enhance tolerance to environmental and metabolic stresses, and optimize cellular performance under specific growth conditions. 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PCC 6803","volume":"13","author":"Wang","year":"2014","journal-title":"Microb. Cell Fact."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jbiotec.2012.03.005","article-title":"Cyanobacterial Biofuel Production","volume":"162","author":"Machado","year":"2012","journal-title":"J. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1128\/AEM.02827-12","article-title":"Metabolic Engineering of Synechocystis Sp. Strain PCC 6803 for Isobutanol Production","volume":"79","author":"Varman","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Muth-Pawlak, D., Kreula, S., Gollan, P.J., Huokko, T., Allahverdiyeva, Y., and Aro, E.M. (2022). Patterning of the Autotrophic, Mixotrophic, and Heterotrophic Proteomes of Oxygen-Evolving Cyanobacterium Synechocystis Sp. PCC 6803. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.891895"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/dnares\/3.3.109","article-title":"Sequence Analysis of the Genome of the Unicellular Cyanobacterium Synechocystis Sp. Strain PCC6803. II. Sequence Determination of the Entire Genome and Assignment of Potential Protein-Coding Regions","volume":"3","author":"Kaneko","year":"1996","journal-title":"DNA Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00343-009-9123-1","article-title":"Effects of Heavy Metals (Pb2+ and Cd2+) on the Ultrastructure, Growth and Pigment Contents of the Unicellular Cyanobacterium Synechocystis Sp. PCC 6803","volume":"27","author":"Arunakumara","year":"2009","journal-title":"Chin. J. Oceanol. Limnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.bbabio.2012.02.035","article-title":"Role of Slr1045 in Environmental Stress Tolerance and Lipid Transport in the Cyanobacterium Synechocystis Sp. PCC6803","volume":"1817","author":"Tahara","year":"2012","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenerg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7419","DOI":"10.1128\/AEM.02694-13","article-title":"Using Transcriptomics to Improve Butanol Tolerance of Synechocystis Sp. Strain PCC 6803","volume":"79","author":"Anfelt","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zav\u0159el, T., O\u010den\u00e1\u0161ov\u00e1, P., and \u010cerven\u00fd, J. (2017). Phenotypic Characterization of Synechocystis Sp. PCC 6803 Substrains Reveals Differences in Sensitivity to Abiotic Stress. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189130"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11120-020-00759-2","article-title":"Characterization of Sll1558 in Environmental Stress Tolerance of Synechocystis Sp. PCC 6803","volume":"146","author":"Uchiyama","year":"2020","journal-title":"Photosynth. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1021\/acssynbio.7b00297","article-title":"A Genetic Toolbox for Modulating the Expression of Heterologous Genes in the Cyanobacterium Synechocystis Sp. PCC 6803","volume":"7","author":"Wang","year":"2017","journal-title":"ACS Synth. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s42003-025-08164-y","article-title":"Development of a CRISPR Activation System for Targeted Gene Upregulation in Synechocystis Sp. PCC 6803","volume":"8","author":"Bourgade","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Satta, A., Esquirol, L., and Ebert, B.E. (2023). Current Metabolic Engineering Strategies for Photosynthetic Bioproduction in Cyanobacteria. Microorganisms, 11.","DOI":"10.3390\/microorganisms11020455"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymben.2019.08.004","article-title":"The Emergence of Adaptive Laboratory Evolution as an Efficient Tool for Biological Discovery and Industrial Biotechnology","volume":"56","author":"Sandberg","year":"2019","journal-title":"Metab. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, Y., Wu, Y., Fan, Y., Zhu, C., Fu, X., Chu, Y., Chen, F., Sun, H., and Mou, H. (2021). Application of Microalgal Stress Responses in Industrial Microalgal Production Systems. Mar. Drugs, 20.","DOI":"10.3390\/md20010030"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107795","DOI":"10.1016\/j.biotechadv.2021.107795","article-title":"Adaptive Laboratory Evolution Principles and Applications in Industrial Biotechnology","volume":"54","author":"Mavrommati","year":"2022","journal-title":"Biotechnol. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1021\/acssynbio.2c00375","article-title":"Inducible CRISPR\/Cas9 Allows for Multiplexed and Rapidly Segregated Single-Target Genome Editing in Synechocystis Sp. PCC 6803","volume":"11","author":"Cengic","year":"2022","journal-title":"ACS Synth. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.copbio.2009.05.011","article-title":"Energy Biotechnology with Cyanobacteria","volume":"20","author":"Angermayr","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/jimb\/kuac023","article-title":"Recent Progress in Adaptive Laboratory Evolution of Industrial Microorganisms","volume":"50","author":"Wang","year":"2023","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kamravamanesh, D., Lackner, M., and Herwig, C. (2018). Bioprocess Engineering Aspects of Sustainable Polyhydroxyalkanoate Production in Cyanobacteria. Bioengineering, 5.","DOI":"10.3390\/bioengineering5040111"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1475-2859-12-64","article-title":"Adaptive Laboratory Evolution\u2014Principles and Applications for Biotechnology","volume":"12","author":"Dragosits","year":"2013","journal-title":"Microb. Cell Fact."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"793","DOI":"10.4014\/jmb.2003.03072","article-title":"Current Status and Applications of Adaptive Laboratory Evolution in Industrial Microorganisms","volume":"30","author":"Lee","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29503","DOI":"10.1038\/srep29503","article-title":"Evolutionary Pressures on Microbial Metabolic Strategies in the Chemostat","volume":"6","author":"Wortel","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"ovad077","DOI":"10.1093\/lambio\/ovad077","article-title":"Engineering Xylose Fermentation in an Industrial Yeast: Continuous Cultivation as a Tool for Selecting Improved Strains","volume":"76","author":"Basso","year":"2023","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nrg3564","article-title":"Genome Dynamics during Experimental Evolution","volume":"14","author":"Barrick","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrg1088","article-title":"Evolution Experiments with Microorganisms: The Dynamics and Genetic Bases of Adaptation","volume":"4","author":"Elena","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hirasawa, T., and Maeda, T. (2022). Adaptive Laboratory Evolution of Microorganisms: Methodology and Application for Bioproduction. Microorganisms, 11.","DOI":"10.3390\/microorganisms11010092"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhang, B., Wu, J., and Meng, F. (2021). Adaptive Laboratory Evolution of Microalgae: A Review of the Regulation of Growth, Stress Resistance, Metabolic Processes, and Biodegradation of Pollutants. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.737248"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/msb.2010.33","article-title":"Regulatory and Metabolic Rewiring during Laboratory Evolution of Ethanol Tolerance in E. coli","volume":"6","author":"Goodarzi","year":"2010","journal-title":"Mol. Syst. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1126\/science.1258137","article-title":"Biofuels. Altered Sterol Composition Renders Yeast Thermotolerant","volume":"346","author":"Caspeta","year":"2014","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1073\/pnas.1219574110","article-title":"Mutation Rate Dynamics in a Bacterial Population Reflect Tension between Adaptation and Genetic Load","volume":"110","author":"Wielgoss","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1021\/acssynbio.1c00337","article-title":"Escherichia coli Data-Driven Strain Design Using Aggregated Adaptive Laboratory Evolution Mutational Data","volume":"10","author":"Phaneuf","year":"2021","journal-title":"ACS Synth. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.cell.2016.02.004","article-title":"Engineering Cellular Metabolism","volume":"164","author":"Nielsen","year":"2016","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1128\/jb.171.6.3449-3457.1989","article-title":"Insertional Mutagenesis by Random Cloning of Antibiotic Resistance Genes into the Genome of the Cyanobacterium synechocystis Strain PCC 6803","volume":"171","author":"Labarre","year":"1989","journal-title":"J. Bacteriol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1038\/s41467-020-15491-7","article-title":"Pooled CRISPRi Screening of the Cyanobacterium Synechocystis Sp PCC 6803 for Enhanced Industrial Phenotypes","volume":"11","author":"Yao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11274-020-02946-8","article-title":"Adaptive Laboratory Evolution for Growth Coupled Microbial Production","volume":"36","author":"Godara","year":"2020","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lee, D.H., Feist, A.M., Barrett, C.L., and Palsson, B. (2011). Cumulative Number of Cell Divisions as a Meaningful Timescale for Adaptive Laboratory Evolution of Escherichia coli. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026172"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nature18959","article-title":"Tempo and Mode of Genome Evolution in a 50,000-Generation Experiment","volume":"536","author":"Tenaillon","year":"2016","journal-title":"Nature"},{"key":"ref_39","unstructured":"Lenski, R.E., Rose, M.R., Simpson, S.C., and Tadler, S.C. (2026, June 09). Long-Term Experimental Evolution in Escherichia coli. I. Adaptation and Divergence During 2000 Generations. Available online: http:\/\/www.jstor.org\/stable\/2462549."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s13068-017-0996-5","article-title":"Identification of Alcohol Stress Tolerance Genes of Synechocystis Sp. PCC 6803 Using Adaptive Laboratory Evolution","volume":"10","author":"Matsusako","year":"2017","journal-title":"Biotechnol. Biofuels"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1021\/acssynbio.5c00344","article-title":"Isolation of Synechocystis Mutants Overproducing Mannitol Directly from CO2 via Laboratory Evolution under Increasing Salt Concentration","volume":"14","author":"Wu","year":"2025","journal-title":"ACS Synth. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ymben.2020.09.005","article-title":"Adaptive Laboratory Evolution of Escherichia coli Lacking Cellular Byproduct Formation for Enhanced Acetate Utilization through Compensatory ATP Consumption","volume":"62","author":"Seong","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00253-021-11730-z","article-title":"Evolutionary and Reverse Engineering to Increase Saccharomyces Cerevisiae Tolerance to Acetic Acid, Acidic PH, and High Temperature","volume":"106","author":"Caspeta","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhang, J., Jin, B., Fu, J., Wang, Z., and Chen, T. (2022). Adaptive Laboratory Evolution of Halomonas bluephagenesis Enhances Acetate Tolerance and Utilization to Produce Poly(3-Hydroxybutyrate). Molecules, 27.","DOI":"10.3390\/molecules27093022"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1038\/s41467-026-72689-x","article-title":"Improving Tolerance to Fluctuating Light through Adaptive Laboratory Evolution in the Cyanobacterium Synechocystis","volume":"17","author":"Chen","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1099\/mic.0.000264","article-title":"The Ploidy Level of Synechocystis Sp. PCC 6803 Is Highly Variable and Is Influenced by Growth Phase and by Chemical and Physical External Parameters","volume":"162","author":"Zerulla","year":"2016","journal-title":"Microbiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103981","DOI":"10.1016\/j.algal.2025.103981","article-title":"The Chromosome Partitioning Protein ParB Influences the Polyploidy of Synechocystis Sp. PCC 6803","volume":"88","author":"Wang","year":"2025","journal-title":"Algal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41477-021-00904-2","article-title":"Enhancing Photosynthesis at High Light Levels by Adaptive Laboratory Evolution","volume":"7","author":"Dann","year":"2021","journal-title":"Nat. Plants"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s42003-021-01875-y","article-title":"Mutations in Hik26 and Slr1916 Lead to High-Light Stress Tolerance in Synechocystis Sp. PCC6803","volume":"4","author":"Yoshikawa","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101856","DOI":"10.1016\/j.algal.2020.101856","article-title":"Divergent Metabolic and Transcriptomic Responses of Synechocystis Sp. PCC 6803 to Salt Stress after Adaptive Laboratory Evolution","volume":"47","author":"Hu","year":"2020","journal-title":"Algal Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"128140","DOI":"10.1016\/j.micres.2025.128140","article-title":"Enhanced Salt Tolerance in Synechocystis Sp. PCC 6803 through Adaptive Evolution: Mechanisms and Applications for Environmental Bioremediation","volume":"296","author":"Zhu","year":"2025","journal-title":"Microbiol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s13068-018-1205-x","article-title":"Adaptive Laboratory Evolution of Cadmium Tolerance in Synechocystis Sp. PCC 6803","volume":"11","author":"Xu","year":"2018","journal-title":"Biotechnol. Biofuels"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cjche.2024.05.023","article-title":"Identification of Genes Involved in Cadmium-Ion Tolerance in Evolutionary Synechocystis Sp. PCC 6803 Tolerant to Both Cadmium and High Light","volume":"74","author":"Xiong","year":"2024","journal-title":"Chin. J. Chem. Eng."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11120-015-0111-3","article-title":"Genomic Analysis of Parallel-Evolved Cyanobacterium Synechocystis Sp. PCC 6803 under Acid Stress","volume":"125","author":"Uchiyama","year":"2015","journal-title":"Photosynth. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tillich, U.M., Wolter, N., Franke, P., D\u00fchring, U., and Frohme, M. (2014). Screening and Genetic Characterization of Thermo-Tolerant Synechocystis Sp. PCC6803 Strains Created by Adaptive Evolution. BMC Biotechnol., 14.","DOI":"10.1186\/1472-6750-14-66"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"111384","DOI":"10.1016\/j.plaphy.2026.111384","article-title":"Mutations in AtpB and LexA Confer Temperature Tolerance in an Evolved Synechocystis Sp. PCC 6803 Strain Resistant to High Temperature and Light","volume":"235","author":"Wang","year":"2026","journal-title":"Plant Physiol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104327","DOI":"10.1016\/j.algal.2025.104327","article-title":"Tolerance Evolution in Cyanobacteria under Chronic Copper and Moxifloxacin Stress: Phenotypic Plasticity and Genomic Fixation","volume":"91","author":"Hou","year":"2025","journal-title":"Algal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"kiag121","DOI":"10.1093\/plphys\/kiag121","article-title":"Genome-Wide Hypermutation-Engineered Synechocystis Sp. PCC 6803 Reveals Membrane-Mediated Triclosan Resistance","volume":"200","author":"Wu","year":"2026","journal-title":"Plant Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103724","DOI":"10.1016\/j.algal.2024.103724","article-title":"Molecular Insights into the Enhanced Growth of Cyanobacteria by Adaptive Laboratory Evolution in Wastewater Environments","volume":"83","author":"Hu","year":"2024","journal-title":"Algal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymben.2023.06.014","article-title":"Laboratory Evolution of Synechocystis Sp. PCC 6803 for Phenylpropanoid Production","volume":"79","author":"Kukil","year":"2023","journal-title":"Metab. Eng."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hosoda, K., Habuchi, M., Suzuki, S., Miyazaki, M., Takikawa, G., Sakurai, T., Kashiwagi, A., Sueyoshi, M., Matsumoto, Y., and Kiuchi, A. (2014). Adaptation of a Cyanobacterium to a Biochemically Rich Environment in Experimental Evolution as an Initial Step toward a Chloroplast-Like State. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098337"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1038\/s41467-026-74903-2","article-title":"Photosystem I-Independent Oxygenic Photosynthesis in Cyanobacteria","volume":"17","author":"Ludwiczak","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10265-011-0454-6","article-title":"Acclimation to High-Light Conditions in Cyanobacteria: From Gene Expression to Physiological Responses","volume":"125","author":"Muramatsu","year":"2011","journal-title":"J. Plant Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3390\/life5010025","article-title":"Salt Acclimation of Cyanobacteria and Their Application in Biotechnology","volume":"5","author":"Pade","year":"2014","journal-title":"Life"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.biortech.2017.05.058","article-title":"Abiotic Stresses as Tools for Metabolites in Microalgae","volume":"244","author":"Paliwal","year":"2017","journal-title":"Bioresour. Technol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2478\/intox-2014-0009","article-title":"Toxicity, Mechanism and Health Effects of Some Heavy Metals","volume":"7","author":"Jaishankar","year":"2014","journal-title":"Interdiscip. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.scitotenv.2014.10.121","article-title":"Heavy Metal Contamination of Soil and Water in the Vicinity of an Abandoned E-Waste Recycling Site: Implications for Dissemination of Heavy Metals","volume":"506\u2013507","author":"Wu","year":"2015","journal-title":"Sci. Total Environ."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Sun, T., Xu, L., Wu, L., Song, Z., Chen, L., and Zhang, W. (2017). Identification of a New Target Slr0946 of the Response Regulator Sll0649 Involving Cadmium Tolerance in Synechocystis Sp. PCC 6803. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01582"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s13068-018-1181-1","article-title":"Recent Developments in Synthetic Biology and Metabolic Engineering in Microalgae towards Biofuel Production","volume":"11","author":"Jagadevan","year":"2018","journal-title":"Biotechnol. Biofuels"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jhazmat.2015.02.012","article-title":"Enhanced Removal of Zn2+ or Cd2+ by the Flocculating Chlorella Vulgaris JSC-7","volume":"289","author":"Alam","year":"2015","journal-title":"J. Hazard. Mater."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.chemosphere.2017.10.017","article-title":"Effect of Cadmium Accumulation on Green Algae Chlamydomonas Reinhardtii and Acid-Tolerant Chlamydomonas CPCC 121","volume":"191","author":"Samadani","year":"2018","journal-title":"Chemosphere"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ruan, G., Mi, W., Yin, X., Song, G., and Bi, Y. (2022). Molecular Responses Mechanism of Synechocystis Sp. PCC 6803 to Cadmium Stress. Water, 14.","DOI":"10.3390\/w14244032"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15171\/bi.2017.01","article-title":"Carotenoids from Microalgae to Block Oxidative Stress","volume":"7","author":"Zuluaga","year":"2017","journal-title":"Bioimpacts"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"162030","DOI":"10.1016\/j.scitotenv.2023.162030","article-title":"Acid Rain Reduces Plant-Photosynthesized Carbon Sequestration and Soil Microbial Network Complexity","volume":"873","author":"Liu","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s13280-019-01244-4","article-title":"Acid Rain and Air Pollution: 50 Years of Progress in Environmental Science and Policy","volume":"49","author":"Grennfelt","year":"2019","journal-title":"Ambio"},{"key":"ref_76","first-page":"126","article-title":"Engineering Escherichia coli to Overproduce Aromatic Amino Acids and Derived Compounds","volume":"13","author":"Rodriguez","year":"2014","journal-title":"Microb. Cell Fact."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11274-025-04264-3","article-title":"Production of Aromatic Amino Acids and Their Derivatives by Escherichia coli and Corynebacterium glutamicum","volume":"41","author":"Hirasawa","year":"2025","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Niraula, A., Danesh, A., Merindol, N., Meddeb-Mouelhi, F., and Desgagn\u00e9-Penix, I. (2025). Aromatic Amino Acids: Exploring Microalgae as a Potential Biofactory. BioTech, 14.","DOI":"10.3390\/biotech14010006"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ymben.2019.11.002","article-title":"Metabolic Engineering of Synechocystis Sp. PCC 6803 for the Production of Aromatic Amino Acids and Derived Phenylpropanoids","volume":"57","author":"Brey","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"136802","DOI":"10.1016\/j.jclepro.2023.136802","article-title":"Evaluation of the Role of Clean Energy Technologies, Human Capital, Urbanization, and Income on the Environmental Quality in the United States","volume":"402","author":"Pata","year":"2023","journal-title":"J. Clean. Prod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"19182","DOI":"10.1038\/s41598-023-46293-8","article-title":"Metabolic Engineering of Saccharomyces Cerevisiae for Second-Generation Ethanol Production from Xylo-Oligosaccharides and Acetate","volume":"13","author":"Lee","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1128\/AEM.65.2.523-528.1999","article-title":"Ethanol Synthesis by Genetic Engineering in Cyanobacteria","volume":"65","author":"Deng","year":"1999","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1039\/b811937f","article-title":"Metabolic Engineering of Cyanobacteria for Ethanol Production","volume":"2","author":"Dexter","year":"2009","journal-title":"Energy Environ. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/jctb.2065","article-title":"Genome-Scale Modeling of Synechocystis Sp. PCC 6803 and Prediction of Pathway Insertion","volume":"84","author":"Fu","year":"2009","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9857","DOI":"10.1039\/C2EE22675H","article-title":"Photosynthetic Production of Ethanol from Carbon Dioxide in Genetically Engineered Cyanobacteria","volume":"5","author":"Gao","year":"2012","journal-title":"Energy Environ. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jbiotec.2012.07.193","article-title":"Physiological Tolerance and Stoichiometric Potential of Cyanobacteria for Hydrocarbon Fuel Production","volume":"162","author":"Knoop","year":"2012","journal-title":"J. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.biotechadv.2014.02.001","article-title":"Engineering Biofuel Tolerance in Non-Native Producing Microorganisms","volume":"32","author":"Jin","year":"2014","journal-title":"Biotechnol. Adv."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1002\/biot.200700168","article-title":"Biobutanol: An Attractive Biofuel","volume":"2","year":"2007","journal-title":"Biotechnol. J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"22168","DOI":"10.1038\/srep22168","article-title":"The Transcriptional Landscape of the Photosynthetic Model Cyanobacterium Synechocystis Sp. PCC6803","volume":"6","author":"Semeniuk","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1128\/AEM.02246-14","article-title":"Use of Adaptive Laboratory Evolution to Discover Key Mutations Enabling Rapid Growth of Escherichia coli K-12 MG1655 on Glucose Minimal Medium","volume":"81","author":"LaCroix","year":"2015","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"D1164","DOI":"10.1093\/nar\/gky983","article-title":"ALEdb 1.0: A Database of Mutations from Adaptive Laboratory Evolution Experimentation","volume":"47","author":"Phaneuf","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1574-6968.2011.02368.x","article-title":"Ploidy in Cyanobacteria","volume":"323","author":"Griese","year":"2011","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pope, M.A., Hodge, J.A., and Nixon, P.J. (2020). An Improved Natural Transformation Protocol for the Cyanobacterium Synechocystis Sp. PCC 6803. Front. Plant Sci., 11.","DOI":"10.3389\/fpls.2020.00372"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1021\/acssynbio.1c00269","article-title":"Exploiting Polyploidy for Markerless and Plasmid-Free Genome Engineering in Cyanobacteria","volume":"10","author":"Jones","year":"2021","journal-title":"ACS Synth. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Jones, P.R. (2014). Genetic Instability in Cyanobacteria\u2014An Elephant in the Room?. Front. Bioeng. Biotechnol., 2.","DOI":"10.3389\/fbioe.2014.00012"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.biteb.2019.02.010","article-title":"Process Simulation and Techno-Economic Assessment for Direct Production of Advanced Bioethanol Using a Genetically Modified Synechocystis Sp","volume":"6","author":"Lopes","year":"2019","journal-title":"Bioresour. Technol. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.egyr.2019.09.016","article-title":"Techno-Economic Assessment of a Synechocystis Based Biorefinery through Process Optimization","volume":"6","author":"Brazinha","year":"2020","journal-title":"Energy Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102454","DOI":"10.1016\/j.algal.2021.102454","article-title":"A Probabilistic Economic and Environmental Impact Assessment of a Cyanobacteria-Based Biorefinery","volume":"59","author":"Beattie","year":"2021","journal-title":"Algal Res."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1836\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:19:14Z","timestamp":1787285954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":98,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["microorganisms14081836"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14081836","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}