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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (11): 92-104    DOI: 10.13523/j.cb.2305009
    
Application of Evolutionary Engineering in Cyanobacterial Biology and Biotechnology Research
MA Yi-fan1,2,3,SUN Hui-li3,4,5,**(),MAO Shao-ming1,2,**(),LUAN Guo-dong3,4,5,LV Xue-feng3,4,5
1 College of Life Science and Technology, Central South University of Forestry and Technology, Changsha 410004, China
2 Hunan Provincial Key Laboratory of Forestry Biotechnology, Central South University of Forestry & Technology, Changsha 410004, China
3 Key Laboratory of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China
4 Shandong Energy Institute, Qingdao 266101, China
5 Qingdao New Energy Shandong Laboratory, Qingdao 266101, China
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Abstract  

Cyanobacteria have long been used as model organisms in basic biological research on topics such as photosynthesis, chloroplast origins and plant evolution. Additionally, due to their fast growth, simple culture techniques and convenient genetic manipulation, cyanobacteria have gained increasing attention in photosynthetic bio-manufacturing. One strategy for studying cyanobacteria is to first obtain mutants with specific phenotypes, and then further analyze their functional mutations and related mechanisms. Moreover, in the development of photosynthetic biomanufacturing technologies, enhancing the physiological tolerance of chassis cells is of significant importance for the large-scale application of cyanobacteria photosynthetic cell factories. Evolutionary engineering offers significant advantages in the acquisition of mutants and the optimization of complex physiological tolerance phenotypes, as it does not require knowledge of the microbial genetic background and metabolic network. This paper reviews the progress of evolutionary engineering in the analysis of cyanobacteria physiological metabolism mechanisms and the optimization of physiological tolerance in cyanobacteria photosynthetic biomanufacturing chassis, and meanwhile it also discusses the challenges and future directions of evolutionary engineering in cyanobacteria applications.

Key words： Cyanobacteria      Evolutionary engineering      Physiological tolerance      Adaptive evolution      Photosynthesis     
Received: 06 May 2023      Published: 01 December 2023
ZTFLH:  Q93-3  
Corresponding Authors: **Hui-li SUN,Shao-ming MAO     E-mail: sunhl@qibebt.ac.cn;msm526@163.com
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MA Yi-fan
SUN Hui-li
MAO Shao-ming
LUAN Guo-dong
LV Xue-feng
Cite this article:

MA Yi-fan, SUN Hui-li, MAO Shao-ming, LUAN Guo-dong, LV Xue-feng. Application of Evolutionary Engineering in Cyanobacterial Biology and Biotechnology Research. China Biotechnology, 2023, 43(11): 92-104.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2305009     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I11/92

类型 策略 优点 缺点
自发突变 在选择压力下进行长期连续传代以积累自发突变 利用自然存在的变异机制,无须额外实验干预,技术难度低 1.进化周期长;2.人力成本较高;3.变异位点随机,无法控制变异范围
理化诱变 使用最佳剂量的UV、MNNG、MMS或EMS对细胞进行诱变处理,然后在特定选择压力下筛选或在逐渐升高的选择压力下进行传代,在传代中通常结合多种理化诱变因子进行多轮处理 丰富变异类型,提高突变频率 1.造成大量细胞损伤,降低效率;2.引入大量变异,其中可能包括较多的无用或不利突变;3.变异位点随机,无法控制变异范围
转座子诱变 构建体内转座子标记诱变系统,然后在特定选择压力下筛选,或直接观测特定表型并筛选 1.可以引发随机或定向突变;2.便于定位转座子的插入基因或位置 1.转座子插入位置可能具有一定偏好性,限制突变范围;2.多数会导致基因表达中断,偶尔会引发蛋白质功能改变,因此变异类型有限;3.对基因组进行饱和突变的成本较高
CRISPRi
抑制文库		 合成针对目标基因或目标途径的gRNA,构建CRISPRi文库并转化蓝细菌构建突变体文库。然后在特定选择压力下筛选,或直接观测特定表型并筛选 能够对特定基因或途径进行精确抑制 1.只能导致基因抑制;2.针对大范围基因设计合成gRNA的成本较高
超突变技术 敲除或过表达细胞复制保真机制中的关键基因,并使用环境胁迫诱发细胞的超突变状态,然后在特定选择压力下筛选,或在逐渐升高的选择压力下进行传代培养 1.较高突变率可以缩短进化周期,并提高进化效率;2.边诱变边筛选的体内连续诱变方式减少了人工干预;3.引入突变的方式较为温和,筛选获得的进化藻株中无用或不利突变较少 1.变异位点随机,无法控制变异范围;2.面对不同胁迫类型和胁迫强度,需要探索适配的突变率强度
Table 1 Comparison of advantages and disadvantages of different mutation introduction methods
Fig.1 Schematic diagram of physicochemical mutagenesis, transposon mutagenesis, pooled CRISPRi screening and hypermutation system
出发藻株 胁迫因素 改造情况 传代时长 进化方法 引文
Synechocystis sp. PCC 6803 微氧条件 微氧条件下生长缺陷 - 转座子诱变 [25]
Leptolyngbya boryana 固氮异常 微氧固氮下生长缺陷 - 转座子诱变 [26]
Synechococcus sp. PCC 7942 DCMU 在1 μmol/L DCMU条件下存活 - MNNG诱变 [36]
Synechococcus sp. PCC 7942 Cyanobacterin 4.7 μmol/L Cyanobacterin条件下生长没有受到抑制 MNNG诱变 [37]
Synechococcus sp. PCC 7942 Bentazone 在含有0.1 mmol/L Bentazone的固体培养基中存活 MNNG诱变 [38]
Synechococcus leopoliensis和Anabaena variabilis 高浓度CO2 失败 750代 自发突变 [39]
Trichodesmium erytheum 高浓度CO2 固氮速率和生长速率提高 4.5年 自发突变 [40]
Nodularia spumigena
strain AV2		 噬藻体 在噬藻体存在条件下不发生裂解 22周 自发突变 [41]
Synechocystis sp. PCC 6803 有毒氨基酸 在含有1 mmol/L精氨酸、组氨酸、赖氨酸、甲硫氨酸、苯丙氨酸、苏氨酸的TCM培养基中维持正常生长速率 160天 自发突变 [42]
Synechococcus sp. PCC 7942 2-nonanone 在100 μmol/L 2-壬烷酮条件下存活 - 转座子诱变 [28]
Synechococcus sp. PCC 7942 缺氮或缺硫 缺氮或缺硫条件下呈现非漂白表型 - 转座子诱变 [8]
Microcystis aeruginosa 高盐 对NaCl的耐受性从10 g/L提高至14 g/L 约160天 自发突变 [43]
Table 2 Application of evolutionary engineering to basic biology of cyanobacteria
出发藻株 改造表型 改造情况 改造时长 进化方法 引用
Synechocystis sp. PCC 6803 丁醇 在0.5%(V/V)丁醇浓度下的生长没有受到抑制 395天 自发突变 [48]
异丁醇 在5 g/L异丁醇条件下能够生长 76天 自发突变 [49]
高盐 3% NaCl条件下的生长速率最高为野生型的150% 303天 自发突变 [50]
高光 能够在9 000 μmol photons/(m2·s)光照下生长 52天 自发突变 [52]
高光 能够在3 000 μmol photons/(m2·s)光照下生长 900多天 UV和MMS诱变结合适应性进化 [23]
高温 能够在45℃/23~26℃的日夜循环条件下稳定生长 1年 适应性进化结合MMS诱变和UV诱变 [53]
酸 能在pH 5.5条件下生长 3个月 自发突变 [51]
Synechococcus sp. PCC 7942 高温高光 极端温度和光照条件下[45℃、1 500 μmol photons/(m2·s)]快速生长 2周内 超突变系统体内连续诱变 [31]
Synechococcus elongatus PCC11801 正丁醇和
2,3-丁二醇		 正丁醇耐受进化藻株表现出对乙醇(22 g/L)、异丙醇(18 g/L)、异丁醇(8 g/L)的交叉耐受性,2,3-丁二醇耐受进化藻株表现出对乙醇(22 g/L)、异丙醇(15 g/L)、正丁醇(4 g/L)、异丁醇(7 g/L)、叔丁醇(15 g/L)、异戊醇(5 g/L)的交叉耐受性 500多天 自发突变 [61]
Anabaena sp. PCC 7120, Anabaena variabilis ATCC 29413, Nostoc punctiforme ATCC 29133 法呢烯、
月桂烯、
芳樟醇
和柠檬烯		 Anabaena sp. PCC 7120对法呢烯的耐受性提高至0.32 g/L,Anabaena variabilis ATCC 29413对芳樟醇的耐受性提高至0.72 g/L,Nostoc punctiforme ATCC 29133对芳樟醇的耐受性提高至0.54 g/L - 自发突变 [65]
Fremyella diplosiphon 高盐 在20 g/L NaCl液体培养基中的生长没有受到抑制 - 高温诱导突变 [66]
Table 3 Application of evolutionary engineering to the optimization of physiological tolerance of cyanobacteria
[1]   Sandberg T E, Salazar M J, Weng L L, et al. The emergence of adaptive laboratory evolution as an efficient tool for biological discovery and industrial biotechnology. Metabolic Engineering, 2019, 56: 1-16.
doi: S1096-7176(19)30153-3 pmid: 31401242
[2]   Novick A, Szilard L.Experiments with the Chemostat on spontaneous mutations of bacteria. Proceedings of the National Academy of Sciences of the United States of America, 1950, 36(12): 708-719.
[3]   LaPanse A J, Krishnan A, Posewitz M C. Adaptive Laboratory Evolution for algal strain improvement: methodologies and applications. Algal Research, 2021, 53: 102122.
doi: 10.1016/j.algal.2020.102122
[4]   Lee S, Kim P. Current status and applications of adaptive laboratory evolution in industrial microorganisms. Journal of Microbiology and Biotechnology, 2020, 30(6): 793-803.
doi: 10.4014/jmb.2003.03072 pmid: 32423186
[5]   Osanai T, Kanesaki Y, Nakano T, et al. Positive regulation of sugar catabolic pathways in the cyanobacterium Synechocystis sp. PCC 6803 by the group 2 σ factor SigE. Journal of Biological Chemistry, 2005, 280(35): 30653-30659.
doi: 10.1074/jbc.M505043200
[6]   Kanan M W, Rozenman M M, Sakurai K, et al. Reaction discovery enabled by DNA-templated synthesis and in vitro selection. Nature, 2004, 431(7008): 545-549.
doi: 10.1038/nature02920
[7]   Kremer B, Kaźmierczak J.Cellularly preserved microbial fossils from -3.4Ga deposits of South Africa: a testimony of early appearance of oxygenic life? Precambrian Research, 2017, 295: 117-129.
doi: 10.1016/j.precamres.2017.04.023
[8]   Lyons T W, Reinhard C T, Planavsky N J. The rise of oxygen in Earth’s early ocean and atmosphere. Nature, 2014, 506(7488): 307-315.
doi: 10.1038/nature13068
[9]   Kasting J F, Howard M T. Atmospheric composition and climate on the early Earth. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 2006, 361(1474): 1733-1742.
[10]   Gonzalez-Esquer C R, Shubitowski T B, Kerfeld C A. Streamlined construction of the cyanobacterial CO2-fixing organelle via protein domain fusions for use in plant synthetic biology. The Plant Cell, 2015, 27(9): 2637-2644.
doi: 10.1105/tpc.15.00329 pmid: 26320224
[11]   Stal L J. [49]Nitrogen fixation in cyanobacterial mats. Methods in Enzymology. Amsterdam: Elsevier, 1988: 474-484.
[12]   Martin W, Rujan T, Richly E, et al. Evolutionary analysis of Arabidopsis, cyanobacterial, and chloroplast genomes reveals plastid phylogeny and thousands of cyanobacterial genes in the nucleus. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(19): 12246-12251.
[13]   Howe C J, Barbrook A C, Koumandou V L, et al. Evolution of the chloroplast genome. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 2003, 358(1429): 99-106.
[14]   Sun T, Li S B, Song X Y, et al. Toolboxes for cyanobacteria: recent advances and future direction. Biotechnology Advances, 2018, 36(4): 1293-1307.
doi: S0734-9750(18)30079-X pmid: 29729377
[15]   Li S B, Sun T, Xu C X, et al. Development and optimization of genetic toolboxes for a fast-growing cyanobacterium Synechococcus elongatus UTEX 2973. Metabolic Engineering, 2018, 48: 163-174.
doi: 10.1016/j.ymben.2018.06.002
[16]   Wang B, Eckert C, Maness P C, et al. A genetic toolbox for modulating the expression of heterologous genes in the cyanobacterium Synechocystis sp. PCC 6803. ACS Synthetic Biology, 2018, 7(1): 276-286.
[17]   Lu X F. A perspective: Photosynthetic production of fatty acid-based biofuels in genetically engineered cyanobacteria. Biotechnology Advances, 2010, 28(6): 742-746.
doi: 10.1016/j.biotechadv.2010.05.021 pmid: 20561924
[18]   Melis A. Solar energy conversion efficiencies in photosynthesis: Minimizing the chlorophyll antennae to maximize efficiency. Plant Science, 2009, 177(4): 272-280.
doi: 10.1016/j.plantsci.2009.06.005
[19]   Oliver J W K, Atsumi S. Metabolic design for cyanobacterial chemical synthesis. Photosynthesis Research, 2014, 120(3): 249-261.
doi: 10.1007/s11120-014-9997-4 pmid: 24718968
[20]   Gong J X, Zheng H J, Wu Z J, et al. Genome shuffling: progress and applications for phenotype improvement. Biotechnology Advances, 2009, 27(6): 996-1005.
doi: S0734-9750(09)00108-6 pmid: 19463940
[21]   Xu C X, Sun T, Li S B, et al. Adaptive laboratory evolution of cadmium tolerance in Synechocystis sp. PCC 6803. Biotechnology for Biofuels, 2018, 11(1): 1-15.
doi: 10.1186/s13068-017-1003-x
[22]   Ennis D G. Mutagenesis. Encyclopedia of Life Sciences. Chichester: John Wiley & Sons, Ltd, 2001: 1-8.
[23]   Dann M, Ortiz E M, Thomas M, et al. Enhancing photosynthesis at high light levels by adaptive laboratory evolution. Nature Plants, 2021, 7(5): 681-695.
doi: 10.1038/s41477-021-00904-2 pmid: 33941908
[24]   Watabe K, Mimuro M, Tsuchiya T. Development of a high-frequency in vivo transposon mutagenesis system for Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942. Plant and Cell Physiology, 2014, 55(11): 2017-2026.
doi: 10.1093/pcp/pcu128
[25]   Terauchi K, Sobue R, Furutani Y, et al. Isolation of cyanobacterial mutants exhibiting growth defects under microoxic conditions by transposon tagging mutagenesis of Synechocystis sp. PCC 6803. The Journal of General and Applied Microbiology, 2017, 63(2): 131-138.
doi: 10.2323/jgam.2016.08.004
[26]   Tomatsu C, Uesaka K, Yamakawa H, et al. In vivo transposon tagging in the nonheterocystous nitrogen-fixing cyanobacterium Leptolyngbya boryana. FEBS Letters, 2018, 592(10): 1634-1642.
doi: 10.1002/1873-3468.13079 pmid: 29723391
[27]   Perelman A, Shaltiel J, Sendersky E, et al. Use of flow cytometry for efficient isolation of cyanobacterial mutants deficient in modulation of pigment level. BioTechniques, 2004, 36(6): 948-952.
pmid: 15211744
[28]   Koksharova O A, Popova A A, Plyuta V A, et al. Four new genes of cyanobacterium Synechococcus elongatus PCC 7942 are responsible for sensitivity to 2-nonanone. Microorganisms, 2020, 8(8): 1234.
doi: 10.3390/microorganisms8081234
[29]   Huang C H, Shen C R, Li H, et al. CRISPR interference (CRISPRi) for gene regulation and succinate production in cyanobacterium S. elongatus PCC 7942. Microbial Cell Factories, 2016, 15(1): 1-11.
doi: 10.1186/s12934-015-0402-6
[30]   Yao L, Shabestary K, Björk S M, et al. Pooled CRISPRi screening of the cyanobacterium Synechocystis sp. PCC 6803 for enhanced industrial phenotypes. Nature Communications, 2020, 11(1): 1-13.
doi: 10.1038/s41467-019-13993-7
[31]   Sun H L, Luan G D, Ma Y F, et al. Engineered hypermutation adapts cyanobacterial photosynthesis to combined high light and high temperature stress. Nature Communications, 2023, 14(1): 1-20.
doi: 10.1038/s41467-022-34464-6
[32]   Tillich U M, Wolter N, Franke P, et al. Screening and genetic characterization of thermo-tolerant Synechocystis sp. PCC 6803 strains created by adaptive evolution. BMC Biotechnology, 2014, 14(1): 1-15.
doi: 10.1186/1472-6750-14-1
[33]   Tillich U M, Wolter N, Schulze K, et al. High-throughput cultivation and screening platform for unicellular phototrophs. BMC Microbiology, 2014, 14(1): 1-13.
doi: 10.1186/1471-2180-14-1
[34]   Cao J L, Russo D A, Xie T, et al. A droplet-based microfluidic platform enables high-throughput combinatorial optimization of cyanobacterial cultivation. Scientific Reports, 2022, 12: 15536.
doi: 10.1038/s41598-022-19773-6 pmid: 36109626
[35]   Price S, Kuzhiumparambil U, Pernice M, et al. Enhancement of cyanobacterial PHB production using random chemical mutagenesis with detection through FACS. Bioprocess and Biosystems Engineering, 2023, 46(2): 297-306.
doi: 10.1007/s00449-022-02834-5 pmid: 36571607
[36]   Golden S S, Sherman L A. Biochemical and biophysical characterization of herbicide-resistant mutants of the unicellular cyanobacterium, Anacystis nidulans R2. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1984, 764(2): 239-246.
doi: 10.1016/0005-2728(84)90033-1
[37]   Mallipudi L R, Gleason F K. Characterization of a mutant of Anacystis nidulans r2 resistant to the natural herbicide, cyanobacterin. Plant Science, 1989, 60(2): 149-154.
doi: 10.1016/0168-9452(89)90160-X
[38]   Bagchi S N, Pistorius E, Michel K. A Synechococcus sp. PCC7942 mutant with a higher tolerance towards bentazone. Photosynthesis Research, 2004, 75: 171-182.
doi: 10.1023/A:1022836218176
[39]   Low-Décarie E, Jewell M D, Fussmann G F, et al. Long-term culture at elevated atmospheric CO2 fails to evoke specific adaptation in seven freshwater phytoplankton species. Proceedings Biological Sciences, 2013, 280(1754): 20122598.
[40]   Hutchins D A, Walworth N G, Webb E A, et al. Irreversibly increased nitrogen fixation in Trichodesmium experimentally adapted to elevated carbon dioxide. Nature Communications, 2015, 6(1): 1-7.
[41]   Coloma S E, Dienstbier A, Bamford D H, et al. Newly isolated Nodularia phage influences cyanobacterial community dynamics. Environmental Microbiology, 2017, 19(1): 273-286.
doi: 10.1111/1462-2920.13601 pmid: 27878952
[42]   Hosoda K, Habuchi M, Suzuki S, et al. Adaptation of a cyanobacterium to a biochemically rich environment in experimental evolution as an initial step toward a chloroplast-like state. PLoS One, 2014, 9(5): e98337.
doi: 10.1371/journal.pone.0098337
[43]   Melero-Jiménez I J, Martín-Clemente E, García-Sánchez M J, et al. Adaptation of the toxic freshwater cyanobacterium Microcystis aeruginosa to salinity is achieved by the selection of spontaneous mutants. Phycological Research, 2019, 67(3): 192-201.
doi: 10.1111/pre.12370
[44]   Cairns J, Coloma S, Sivonen K, et al. Evolving interactions between diazotrophic cyanobacterium and phage mediate nitrogen release and host competitive ability. Royal Society Open Science, 2016, 3(12): 160839.
doi: 10.1098/rsos.160839
[45]   Rutherford B J, Dahl R H, Price R E, et al. Functional genomic study of exogenous n-butanol stress in Escherichia coli. Applied and Environmental Microbiology, 2010, 76(6): 1935-1945.
doi: 10.1128/AEM.02323-09 pmid: 20118358
[46]   Portnoy V A, Bezdan D, Zengler K. Adaptive laboratory evolution:harnessing the power of biology for metabolic engineering. Current Opinion in Biotechnology, 2011, 22(4): 590-594.
doi: 10.1016/j.copbio.2011.03.007
[47]   Toepel J, Karande R, Klähn S, et al. Cyanobacteria as whole-cell factories: current status and future prospectives. Current Opinion in Biotechnology, 2023, 80: 102892.
doi: 10.1016/j.copbio.2023.102892
[48]   Wang Y X, Shi M L, Niu X F, et al. Metabolomic basis of laboratory evolution of butanol tolerance in photosynthetic Synechocystis sp. PCC 6803. Microbial Cell Factories, 2014, 13(1): 1-12.
doi: 10.1186/1475-2859-13-1
[49]   Matsusako T, Toya Y, Yoshikawa K, et al. Identification of alcohol stress tolerance genes of Synechocystis sp. PCC 6803 using adaptive laboratory evolution. Biotechnology for Biofuels, 2017, 10(1): 1-9.
doi: 10.1186/s13068-016-0693-9
[50]   Hu L, He J Y, Dong M J, et al. Divergent metabolic and transcriptomic responses of Synechocystis sp. PCC 6803 to salt stress after adaptive laboratory evolution. Algal Research, 2020, 47: 101856.
doi: 10.1016/j.algal.2020.101856
[51]   Uchiyama J, Kanesaki Y, Iwata N, et al. Genomic analysis of parallel-evolved cyanobacterium Synechocystis sp. PCC 6803 under acid stress. Photosynthesis Research, 2015, 125(1): 243-254.
doi: 10.1007/s11120-015-0111-3
[52]   Yoshikawa K, Ogawa K, Toya Y, et al. Mutations in hik26 and slr 1916 lead to high-light stress tolerance in Synechocystis sp. PCC6803. Communications Biology, 2021, 4: 343.
doi: 10.1038/s42003-021-01875-y
[53]   Tillich U M, Lehmann S, Schulze K, et al. The optimal mutagen dosage to induce point-mutations in Synechocystis sp. PCC 6803 and its application to promote temperature tolerance. PLoS One, 2012, 7(11): e49467.
doi: 10.1371/journal.pone.0049467
[54]   Berry S, Esper B, Karandashova I, et al. Potassium uptake in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 mainly depends on a Ktr-like system encoded by slr1509 (ntpJ). FEBS Letters, 2003, 548(1-3): 53-58.
doi: 10.1016/S0014-5793(03)00729-4
[55]   Munns R, Tester M. Mechanisms of salinity tolerance. Annual Review of Plant Biology, 2008, 59: 651-681.
doi: 10.1146/annurev.arplant.59.032607.092911 pmid: 18444910
[56]   Reed R H, Richardson D L, Stewart W D P. Osmotic responses of unicellular blue-green algae (cyanobacteria): changes in cell volume and intracellular solute levels in response to hyperosmotic treatment. Plant, Cell & Environment, 1986, 9(1): 25-31.
[57]   Satta A, Esquirol L, Ebert B E. Current metabolic engineering strategies for photosynthetic bioproduction in cyanobacteria. Microorganisms, 2023, 11(2): 455.
doi: 10.3390/microorganisms11020455
[58]   Gao X Y, Sun T, Pei G S, et al. Cyanobacterial chassis engineering for enhancing production of biofuels and chemicals. Applied Microbiology and Biotechnology, 2016, 100(8): 3401-3413.
doi: 10.1007/s00253-016-7374-2 pmid: 26883347
[59]   Jaiswal D, Sengupta A, Sohoni S, et al. Genome features and biochemical characteristics of a robust, fast growing and naturally transformable cyanobacterium Synechococcus elongatus PCC 11801 isolated from India. Scientific Reports, 2018, 8(1): 1-13.
[60]   Shinjinee S, Damini J, Annesha S, et al. Metabolic engineering of a fast-growing cyanobacterium Synechococcus elongatus PCC 11801 for photoautotrophic production of succinic acid. Biotechnology for Biofuels, 2020, 13(1): 89.
doi: 10.1186/s13068-020-01727-7
[61]   Srivastava V, Amanna R, Rowden S J L, et al. Adaptive laboratory evolution of the fast-growing cyanobacterium Synechococcus elongatus PCC 11801 for improved solvent tolerance. Journal of Bioscience and Bioengineering, 2021, 131(5): 491-500.
doi: 10.1016/j.jbiosc.2020.11.012
[62]   Potapova T V, Koksharova O A. Filamentous cyanobacteria as a prototype of multicellular organisms. Russian Journal of Plant Physiology, 2020, 67(1): 17-30.
doi: 10.1134/S102144372001015X
[63]   Markou G, Georgakakis D. Cultivation of filamentous cyanobacteria (blue-green algae) in agro-industrial wastes and wastewaters: a review. Applied Energy, 2011, 88(10): 3389-3401.
doi: 10.1016/j.apenergy.2010.12.042
[64]   Tan L T. Pharmaceutical agents from filamentous marine cyanobacteria. Drug Discovery Today, 2013, 18(17-18): 863-871.
doi: 10.1016/j.drudis.2013.05.010 pmid: 23711931
[65]   Johnson T J, Halfmann C, Zahler J D, et al. Increasing the tolerance of filamentous cyanobacteria to next-generation biofuels via directed evolution. Algal Research, 2016, 18: 250-256.
doi: 10.1016/j.algal.2016.06.023
[66]   Tabatabai B, Arumanayagam A S, Enitan O, et al. Identification of a halotolerant mutant via in vitro mutagenesis in the cyanobacterium Fremyella diplosiphon. Current Microbiology, 2017, 74(1): 77-83.
doi: 10.1007/s00284-016-1156-z pmid: 27844126
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