Developing Cyanobacterial Quorum Sensing Toolkits: Toward Interspecies Coordination in Mixed Autotroph/Heterotroph Communities
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Abstract
High Resolution Image Download MS PowerPoint Slide There has been substantial recent interest in the promise of sustainable, light-driven bioproduction using cyanobacteria, including developing efforts for microbial bioproduction using mixed autotroph/heterotroph communities, which could provide useful properties, such as division of metabolic labor. However, building stable mixed-species communities of sufficient productivity remains a challenge, partly due to the lack of strategies for synchronizing and coordinating biological activities across different species. To address this obstacle, we developed an inter-species communication system using quorum sensing (QS) modules derived from well-studied pathways in heterotrophic microbes. In the model cyanobacterium, Synechococcus elongatus PCC 7942 ( S. elongatus ), we designed, integrated, and characterized genetic circuits that detect acyl-homoserine lactones (AHLs), diffusible signals utilized in many QS pathways. We showed that these receiver modules sense exogenously supplied AHL molecules and activate gene expression in a dose-dependent manner. We characterized these AHL receiver circuits in parallel with Escherichia coli W ( E. coli W) to dissect species-specific properties, finding broad agreement, albeit with increased basal expression in S. elongatus . Our engineered “sender” E. coli strains accumulated biologically synthesized AHLs within the supernatant and activated receiver strains similarly to exogenous AHL activation. Our results will bolster the design of sophisticated genetic circuits in cyanobacterial/heterotroph consortia and the engineering of QS-like behaviors across cyanobacterial populations.
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Kokarakis et al. demonstrated the first implementation of heterologous acyl-homoserine lactone quorum-sensing pathways (Lux, Las, and Tra) in S. elongatus PCC 7942, showing that these circuits detect AHL signals in a dose-dependent manner and can link E. coli population density to cyanobacterial gene expression outputs, a framework directly applicable to regulating sucrose secretion and other碳
“Kokarakis et al. demonstrated the first implementation of heterologous acyl-homoserine lactone quorum-sensing pathways (Lux, Las, and Tra) in S. elongatus PCC 7942, showing that these circuits detect AHL signals in a dose-dependent manner and can link E. coli population density to cyanobacterial gene expression outputs, a framework directly applicable to regulating sucrose secretion and other”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [111]
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Cites
Enzymatic assembly of DNA molecules up to several hundred kilobases
Gibson, D. G., Young, L., Chuang, R.-Y., Venter, J. C., Hutchison, C. A., & Smith, H. O. (2009) · Nature Methods · doi:10.1038/nmeth.1318 · Cited by 9,742 · see citing works
Miller, M. B., & Bassler, B. L. (2001) · Annual Review of Microbiology · doi:10.1146/annurev.micro.55.1.165 · Cited by 5,127 · see citing works
Fuqua, W. C., Winans, S. C., & Greenberg, E. P. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.2.269-275.1994 · Cited by 2,941 · see citing works
Quorum sensing signal-response systems in Gram-negative bacteria
Papenfort, K., & Bassler, B. L. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.89 · Cited by 2,256 · see citing works
Bacterial quorum sensing in complex and dynamically changing environments
Mukherjee, S., & Bassler, B. L. (2019) · Nature Reviews Microbiology · doi:10.1038/s41579-019-0186-5 · Cited by 1,377 · see citing works
Progress in and promise of bacterial quorum sensing research
Whiteley, M., Diggle, S. P., & Greenberg, E. P. (2017) · Nature · doi:10.1038/nature24624 · Cited by 1,281 · see citing works
A synchronized quorum of genetic clocks
Danino, T., Mondragón-Palomino, O., Tsimring, L. S., & Hasty, J. (2010) · Nature · doi:10.1038/nature08753 · Cited by 987 · see citing works
A brief history of synthetic biology
Cameron, D. E., Bashor, C. J., & Collins, J. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3239 · Cited by 944 · see citing works
Gambello, M. J., & Iglewski, B. H. (1991) · Journal of Bacteriology · doi:10.1128/jb.173.9.3000-3009.1991 · Cited by 710 · see citing works
Programmed population control by cell–cell communication and regulated killing
You, L., Cox, R. S., Weiss, R., & Arnold, F. H. (2004) · Nature · doi:10.1038/nature02491 · Cited by 708 · see citing works
Bacterial bioluminescence: its control and ecological significance
Nealson, K. H., & Hastings, J. W. (1979) · Microbiological Reviews · doi:10.1128/mr.43.4.496-518.1979 · Cited by 688 · see citing works
Acyl-Homoserine Lactone Quorum Sensing: From Evolution to Application
Schuster, M., Sexton, D. J., Diggle, S. P., & Greenberg, E. P. (2013) · Annual Review of Microbiology · doi:10.1146/annurev-micro-092412-155635 · Cited by 549 · see citing works
BglBrick vectors and datasheets: A synthetic biology platform for gene expression
Lee, T. S., Krupa, R. A., Zhang, F., Hajimorad, M., Holtz, W. J., Prasad, N., Lee, S. K., & Keasling, J. D. (2011) · Journal of Biological Engineering · doi:10.1186/1754-1611-5-12 · Cited by 476 · see citing works
[12] Genetic engineering of the cyanobacterial chromosome
Golden, S. S., Brusslan, J. A., & Haselkorn, R. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)53055-5 · Cited by 394 · see citing works
Rerouting Carbon Flux to Enhance Photosynthetic Productivity
Ducat, D. C., Avelar-Rivas, J. A., Way, J. C., & Silver, P. A. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.07901-11 · Cited by 362 · see citing works
Self-citationThe crystal structure of the quorum sensing protein TraR bound to its autoinducer and target DNA
Vannini, A., Volpari, C., Gargioli, C., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf459 · Cited by 356 · see citing works
Zhu, J., & Winans, S. C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1507 · Cited by 345 · see citing works
Engineering microbial consortia for controllable outputs
Lindemann, S. R., Bernstein, H. C., Song, H.-S., Fredrickson, J. K., Fields, M. W., Shou, W., Johnson, D. R., & Beliaev, A. S. (2016) · The ISME Journal · doi:10.1038/ismej.2016.26 · Cited by 340 · see citing works
Designing microbial consortia with defined social interactions
Kong, W., Meldgin, D. R., Collins, J. J., & Lu, T. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0091-7 · Cited by 327 · see citing works
Engineering microbial consortia by division of labor
Roell, G. W., Zha, J., Carr, R. R., Koffas, M. A. G., Fong, S. S., & Tang, Y. (2019) · Microbial Cell Factories · doi:10.1186/s12934-019-1083-3 · Cited by 318 · see citing works
Metabolic division of labor in microbial systems
Tsoi, R., Wu, F., Zhang, C., Bewick, S. A., Karig, D., & You, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716888115 · Cited by 296 · see citing works
Emergent genetic oscillations in a synthetic microbial consortium
Chen, Y., Kim, J. K., Hirning, A. J., Josić́, K., & Bennett, M. R. (2015) · Science · doi:10.1126/science.aaa3794 · Cited by 279 · see citing works
Engineering Cyanobacteria To Synthesize and Export Hydrophilic Products
Niederholtmeyer, H., Wolfstädter, B. T., Savage, D. F., Silver, P. A., & Way, J. C. (2010) · Applied and Environmental Microbiology · doi:10.1128/aem.00202-10 · Cited by 243 · see citing works
Cyanobacteria: Promising biocatalysts for sustainable chemical production
Knoot, C. J., Ungerer, J., Wangikar, P. P., & Pakrasi, H. B. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.815886 · Cited by 225 · see citing works
New applications of synthetic biology tools for cyanobacterial metabolic engineering
Santos-Merino, M., Singh, A. K., & Ducat, D. C. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00033 · Cited by 222 · see citing works
Self-citationQuorum Sensing Communication Modules for Microbial Consortia
Scott, S. R., & Hasty, J. (2016) · ACS Synthetic Biology · doi:10.1021/acssynbio.5b00286 · Cited by 204 · see citing works
Tools for engineering coordinated system behaviour in synthetic microbial consortia
Kylilis, N., Tuza, Z. A., Stan, G.-B. V., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05046-2 · Cited by 201 · see citing works
Core Principles of Bacterial Autoinducer Systems
Hense, B. A., & Schuster, M. (2015) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00024-14 · Cited by 186 · see citing works
Quorum Quenching Agents: Resources for Antivirulence Therapy
Tang, K., & Zhang, X. (2014) · Marine Drugs · doi:10.3390/md12063245 · Cited by 184 · see citing works
Cyanobacterial pigments: Perspectives and biotechnological approaches
Saini, D. K., Pabbi, S., & Shukla, P. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.08.002 · Cited by 184 · see citing works
Sharif, D. I., Gallon, J., Smith, C. J., & Dudley, E. (2008) · The ISME Journal · doi:10.1038/ismej.2008.68 · Cited by 174 · see citing works
The chemical ecology of cyanobacteria
Leão, P. N., Engene, N., Antunes, A., Gerwick, W. H., & Vasconcelos, V. M. (2012) · Natural Product Reports · doi:10.1039/c2np00075j · Cited by 173 · see citing works
Collins, C. H., Arnold, F. H., & Leadbetter, J. R. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04437.x · Cited by 156 · see citing works
Specialized Techniques for Site-Directed Mutagenesis in Cyanobacteria
Clérico, E. M., Ditty, J. L., & Golden, S. S. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-257-1_11 · Cited by 154 · see citing works
Fuqua, C., Burbea, M., & Winans, S. C. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.5.1367-1373.1995 · Cited by 151 · see citing works
Synthetic photosynthetic consortia define interactions leading to robustness and photoproduction
Hays, S. G., Yan, L. L. W., Silver, P. A., & Ducat, D. C. (2017) · Journal of Biological Engineering · doi:10.1186/s13036-017-0048-5 · Cited by 147 · see citing works
Self-citationChoi, S. H., & Greenberg, E. P. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.12.4064-4069.1992 · Cited by 143 · see citing works
Application of bioluminescence to the study of circadian rhythms in cyanobacteria
Andersson, C. R., Tsinoremas, N. F., Shelton, J. L., Lebedeva, N. V., Yarrow, J., Min, H., & Golden, S. S. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)05511-7 · Cited by 142 · see citing works
Synthetic Biology for Manipulating Quorum Sensing in Microbial Consortia
Stephens, K., & Bentley, W. E. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.03.009 · Cited by 130 · see citing works
Long, B., Fischer, B. L., Zeng, Y., Amerigian, Z., Li, Q., Bryant, H. L., Li, M., Dai, S. Y., & Yuan, J. S. (2022) · Nature Communications · doi:10.1038/s41467-021-27665-y · Cited by 124 · see citing works
Santos‐Merino, M., Torrado, A., Davis, G. A., Röttig, A., Bibby, T. S., Kramer, D., & Ducat, D. C. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021523118 · Cited by 109 · see citing works
Self-citationKhan, M. I., Lee, M. G., Shin, J. H., & Kim, J. D. (2017) · AMB Express · doi:10.1186/s13568-016-0320-y · Cited by 78 · see citing works
Orthogonal intercellular signaling for programmed spatial behavior
Grant, P. K., Dalchau, N., Brown, J. R., Federici, F., Rudge, T. J., Yordanov, B., Patange, O., Phillips, A., & Haseloff, J. P. (2016) · Molecular Systems Biology · doi:10.15252/msb.20156590 · Cited by 72 · see citing works
Clay, M. E., Hammond, J. H., Zhong, F., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1917576117 · Cited by 70 · see citing works
Increased Photochemical Efficiency in Cyanobacteria via an Engineered Sucrose Sink
Abramson, B. W., Kachel, B., Kramer, D., & Ducat, D. C. (2016) · Plant and Cell Physiology · doi:10.1093/pcp/pcw169 · Cited by 67 · see citing works
Self-citationEngineering cyanobacteria chassis cells toward more efficient photosynthesis
Luan, G., Zhang, S., & Lü, X. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.07.004 · Cited by 66 · see citing works
Engineering the esaR Promoter for Tunable Quorum Sensing-Dependent Gene Expression
Shong, J., & Collins, C. H. (2013) · ACS Synthetic Biology · doi:10.1021/sb4000433 · Cited by 56 · see citing works
Cordara, A., Re, A., Pagliano, C., Van Alphen, P., Pirone, R., Saracco, G., Branco dos Santos, F., Hellingwerf, K., & Vasile, N. (2018) · PeerJ · doi:10.7717/peerj.5256 · Cited by 41 · cited 1× · see citing works
“Dry cell weight measurement Dry cell mass was determined as previously described (Cordara et al., 2018).”
MethodRomero, M., Muro-Pastor, A. M., & Otero, A. (2010) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2010.02175.x · Cited by 40 · see citing works
Wang, S., Ding, P., Lu, S., et al. (2021) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2021.112330 · Cited by 38 · see citing works
Engineering Cyanobacterial Cell Morphology for Enhanced Recovery and Processing of Biomass
Jordan, A., Chandler, J., MacCready, J. S., Huang, J., Osteryoung, K. W., & Ducat, D. C. (2017) · Applied and Environmental Microbiology · doi:10.1128/aem.00053-17 · Cited by 37 · see citing works
Self-citationDoesMicrocystis aeruginosahave quorum sensing?
Zhai, C., Zhang, P., Shen, F., et al. (2012) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2012.02650.x · Cited by 36 · see citing works
Quorum sensing autoinducers: Do they play a role in natural microbial habitats?
Bachofen, R., & Schenk, A. (1998) · Microbiological Research · doi:10.1016/s0944-5013(98)80022-0 · Cited by 35 · see citing works
Nano-guided cell networks as conveyors of molecular communication
Terrell, J. L., Wu, H., Tsao, C., Barber, N. B., Servinsky, M. D., Payne, G. F., & Bentley, W. E. (2015) · Nature Communications · doi:10.1038/ncomms9500 · Cited by 34 · see citing works
Synthetic Biology of Cyanobacteria
(2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0854-3 · Cited by 34 · see citing works
Dynamic patterns of quorum sensing signals in phycospheric microbes during a marine algal bloom
Zhu, J., Chen, G., Zhou, J., Zeng, Y., Cheng, K., & Cai, Z. (2022) · Environmental Research · doi:10.1016/j.envres.2022.113443 · Cited by 33 · see citing works
Harnessing transcription for bioproduction in cyanobacteria
Stensjö, K., Vavitsas, K., & Tyystjärvi, T. (2017) · Physiologia Plantarum · doi:10.1111/ppl.12606 · Cited by 29 · see citing works
Evidence of Quorum Sensing in Cyanobacteria by Homoserine Lactones: The Origin of Blooms
Herrera, N. A., & Echeverri, F. (2021) · Water · doi:10.3390/w13131831 · Cited by 26 · see citing works
Rational Design of an Ultrasensitive Quorum-Sensing Switch
Zeng, W., Du, P., Lou, Q., Wu, L., Zhang, H. M., Lou, C., Wang, H., & Ouyang, Q. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00367 · Cited by 22 · see citing works
Synthetic Biology in Cyanobacteria and Applications for Biotechnology
Hudson, E. P. (2021) · Wiley eBooks · doi:10.1002/9783527824908.ch5 · Cited by 16 · see citing works
Du, W., Caicedo-Burbano, P., Hellingwerf, K. J., & dos Santos, F. B. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0854-3_1 · Cited by 13 · see citing works
Samanamud, G. R. L., Reeves, T. E., Tidwell, M. W., et al. (2021) · Environmental Engineering Science · doi:10.1089/ees.2021.0089 · Cited by 9 · see citing works
Junaid, M., Inaba, Y., Otero, A., & Suzuki, I. (2021) · Journal of Applied Phycology · doi:10.1007/s10811-021-02397-0 · Cited by 5 · see citing works
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Walshe, J., & Saha, S. K. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48060638 · Cited by 1 · see citing works
“…PCC 7942, showing that these circuits detect AHL signals in a dose-dependent manner and can link E. coli population density to cyanobacterial gene expression outputs, a framework directly applicable to regulating sucrose secretion and other carbon transfer events in synthetic co-cultures [111].”
- Authors
- Kokarakis, E. J., Rillema, R., Ducat, D. C., & Sakkos, J. K.
- Affiliations
- Michigan State University (US)
- Corresponding author
- Sakkos, Jonathan K.
- Venue
- ACS Synthetic Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2022-12-27
- Volume
- 12
- Issue
- 1
- Pages
- 265-276
- ISSN
- 2161-5063 (ISSN-L)
- PMC
- PMC9872165
- OpenAlex
- W4312210860
- Cited by
- 21
- References
- 63
- Citations by year
- 2026: 10 · 2025: 3 · 2024: 5 · 2023: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Synthetic Biology (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (DE-FG02-91ER20021)
- National Institute of General Medical Sciences (T32-GM110523)
- National Science Foundation (1845463)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Physical Sciences › Engineering › Biomedical Engineering › Molecular Communication and Nanonetworks
- Keywords
- interspecies communication, Synechococcus elongatus PCC 7942, N-acyl homoserine lactones, synthetic gene circuits, Escherichia coli W, bioproduction, metabolic coordination, synthetic biology
- MeSH terms
- Cyanobacteria, Escherichia coli, Quorum Sensing, Acyl-Butyrolactones
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