Abstract
Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.
Similar content being viewed by others
References
Schlatter C. Environmental pollution and human health. Sci Total Environ. 1994;143(1):93–101.
Rui YK, Kong XB, Qin J. Application of ICP-MS to detection of heavy metals in soil from different crop** systems. Guang Pu Xue Yu Guang Pu Fen **. 2007;27(6):1201–3.
Pyle SM, Nocerino JM. Comparison of AAS, ICP-AES, PSA, and XRF in determining lead and cadmium in soil. Environ Sci Technol. 1995;30(1):204–13.
Turdean GL. Design and development of biosensors for the detection of heavy metal toxicity. Int J Electrochem. 2011; https://doi.org/10.4061/2011/343125.
Yi JM, Chon HT, Park M. Migration and enrichment of arsenic in the rock-soil-crop plant system in areas covered with black shale, Korea. Sci World J. 2003;3:194–8.
Bontidean I, Berggren C, Johansson G, Csoregi E, Mattiasson B, Lloyd JR. Detection of heavy metal ions at femtomolar levels using protein-based biosensors. Anal Chem. 1998;70(19):4162–9.
Blake DA, Jones RM, Blake RC II, Pavlov AR, Darwish IA, Yu H. Antibody-based sensors for heavy metal ions. Biosens Bioelectron. 2001;16(9/12):799–809.
Aragay G, Pons J, Merkoci A. Recent trends in macro-, micro-, and nanomaterial-based tools and strategies for heavy-metal detection. Chem Rev. 2011;111(5):3433–58.
Wu Y, Liu L, Zhan S, Wang F, Zhou P. Ultrasensitive aptamer biosensor for arsenic(III) detection in aqueous solution based on surfactant-induced aggregation of gold nanoparticles. Analyst. 2012;137(18):4171–8.
Lee JS, Han MS, Mirkin CA. Colorimetric detection of mercuric ion (Hg2+) in aqueous media using DNA-functionalized gold nanoparticles. Angew Chem Int Ed Engl. 2007;46(22):4093–6.
Oliveira SC, Corduneanu O, Oliveira-Brett AM. In situ evaluation of heavy metal-DNA interactions using an electrochemical DNA biosensor. Bioelectrochemistry. 2008;72(1):53–8.
Forzani ES, Zhang H, Chen W, Tao N. Detection of heavy metal ions in drinking water using a high-resolution differential surface plasmon resonance sensor. Environ Sci Technol. 2005;39(5):1257–62.
Dzyadevych SV, Soldatkin AP, Korpan YI, Arkhypova VN, El'skaya AV, Chovelon JM. Biosensors based on enzyme field-effect transistors for determination of some substrates and inhibitors. Anal Bioanal Chem. 2003;377(3):496–506.
Malitesta C, Guascito MR. Heavy metal determination by biosensors based on enzyme immobilised by electropolymerisation. Biosens Bioelectron. 2005;20(8):1643–7.
Khosraviani M, Pavlov AR, Flowers GC, Blake DA. Detection of heavy metals by immunoassay: optimization and validation of a rapid, portable assay for ionic cadmium. Environ Sci Technol. 1998;32(1):137–42. https://doi.org/10.1021/es9703943.
Cosnier S, Mousty C, Cui X, Yang X, Dong S. Specific determination of As(V) by an acid phosphatase-polyphenol oxidase biosensor. Anal Chem. 2006;78(14):4985–9.
Zhu X, Xu L, Lou Y, Yu H, Li X, Blake DA. Preparation of specific monoclonal antibodies (MAbs) against heavy metals: MAbs that recognize chelated cadmium ions. J Agric Food Chem. 2007;5(19):7648–53.
Berggren C, Johansson G. Capacitance measurements of antibody-antigen interactions in a flow system. Anal Chem. 1997;69(18):3651–7.
Cherian S, Gupta RK, Mullin BC, Thundat T. Detection of heavy metal ions using protein-functionalized microcantilever sensors. Biosens Bioelectron. 2003;19(5):411–6.
Karube Isao YN. Enzyme sensors for environmental analysis. J Mol Catalysis B Enzymatic. 2000;10(1/3):177–81.
Mehta J, Bhardwaj SK, Bhardwaj N, Paul AK, Kumar P, Kim KH. Progress in the biosensing techniques for trace-level heavy metals. Biotechnol Adv. 2016;34(1):47–60.
Bereza-Malcolm LT, Mann G, Franks AE. Environmental sensing of heavy metals through whole cell microbial biosensors: a synthetic biology approach. ACS Synth Biol. 2015;4(5):535–46.
Park M, Tsai SL, Chen W. Microbial biosensors: engineered microorganisms as the sensing machinery. Sensors (Basel.). 2013;13(5):5777–95.
Shin HJ. Genetically engineered microbial biosensors for in situ monitoring of environmental pollution. Appl Microbiol Biotechnol. 2011;89(4):867–77.
Hynninen A, Virta M. Whole-cell bioreporters for the detection of bioavailable metals. Adv Biochem Eng Biotechnol. 2010;118:31–63.
Das S, Dash HR, Chakraborty J. Genetic basis and importance of metal resistant genes in bacteria for bioremediation of contaminated environments with toxic metal pollutants. Appl Microbiol Biotechnol. 2016;100(7):2967–84.
Lee SJ, Lee DW. Design and development of synthetic microbial platform cells for bioenergy. Front Microbiol. 2013;4:92. https://doi.org/10.3389/fmicb.2013.00092.
Checa SK, Zurbriggen MD, Soncini FC. Bacterial signaling systems as platforms for rational design of new generations of biosensors. Curr Opin Biotechnol. 2012;23(5):766–72.
Siuti P, Yazbek J, Lu TK. Synthetic circuits integrating logic and memory in living cells. Nat Biotechnol. 2013;31(5):448–52.
Purnick PE, Weiss R. The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol. 2009;10(6):410–22.
Bhatia P, Chugh A. Synthetic Biology Based Biosensors and the Emerging Governance Issues. Curr Synth Syst Biol doi. 2013; https://doi.org/10.4172/2332-0737.1000108.
Harms H, Wells MC, van der Meer JR. Whole-cell living biosensors–are they ready for environmental application? Appl Microbiol Biotechnol. 2006;70(3):273–80.
Yagi K. Applications of whole-cell bacterial sensors in biotechnology and environmental science. Appl Microbiol Biotechnol. 2007;73(6):1251–8.
Giedroc DP, Arunkumar AI. Metal sensor proteins: nature's metalloregulated allosteric switches. Dalton Trans. 2007;29:3107–20.
O'Halloran TV. Transition metals in control of gene expression. Science. 1993;261(5122):715–25.
Mahr R, Frunzke J. Transcription factor-based biosensors in biotechnology: current state and future prospects. Appl Microbiol Biotechnol. 2016;100(1):79–90.
Fujimoto H, Wakabayashi M, Yamashiro H, Maeda I, Isoda K, Kondoh M, et al. Whole-cell arsenite biosensor using photosynthetic bacterium Rhodovulum sulfidophilum. Rhodovulum sulfidophilum as an arsenite biosensor. Appl Microbiol Biotechnol. 2006;73(2):332–8.
Wackwitz A, Harms H, Chatzinotas A, Breuer U, Vogne C, Van Der Meer JR. Internal arsenite bioassay calibration using multiple bioreporter cell lines. Microb Biotechnol. 2008;1(2):149–57.
Webster DP, TerAvest MA, Doud DF, Chakravorty A, Holmes EC, Radens CM, et al. An arsenic-specific biosensor with genetically engineered Shewanella oneidensis in a bioelectrochemical system. Biosens Bioelectron. 2014;62:320–4.
Li L, Liang J, Hong W, Zhao Y, Sun S, Yang X, et al. Evolved bacterial biosensor for arsenite detection in environmental water. Environ Sci Technol. 2015;49(10):6149–55.
Merulla D, van der Meer JR. Regulatable and modulable background expression control in prokaryotic synthetic circuits by auxiliary repressor binding sites. ACS Synth Biol. 2016;5(1):36–45.
Hu Q, Li L, Wang Y, Zhao W, Qi H, Zhuang G. Construction of WCB-11: a novel phiYFP arsenic-resistant whole-cell biosensor. J Environ Sci (China). 2010;22(9):1469–74.
Huang CW, Yang SH, Sun MW, Liao VH. Development of a set of bacterial biosensors for simultaneously detecting arsenic and mercury in groundwater. Environ Sci Pollut Res Int. 2015;22(13):10206–13.
Wang B, Barahona M, Buck M. A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals. Biosens Bioelectron. 2013;40(1):368–76.
Wu CH, Le D, Mulchandani A, Chen W. Optimization of a whole-cell cadmium sensor with a toggle gene circuit. Biotechnol Prog. 2009;25(3):898–903.
Joe MH, Lee KH, Lim SY, Im SH, Song HP, Lee IS, et al. Pigment-based whole-cell biosensor system for cadmium detection using genetically engineered Deinococcus radiodurans. Bioprocess Biosyst Eng. 2012;35(1/2):265–72.
Kim HJ, Lim JW, Jeong H, Lee SJ, Lee DW, Kim T, Lee SJ. Development of a highly specific and sensitive cadmium and lead microbial biosensor using synthetic CadC-T7 genetic circuitry. Biosens Bioelectron. 2016;79:701–8.
Shetty RS, Deo SK, Shah P, Sun Y, Rosen BP, Daunert S. Luminescence-based whole-cell-sensing systems for cadmium and lead using genetically engineered bacteria. Anal Bioanal Chem. 2003;376(1):11–7.
Tauriainen S, Karp M, Chang W, Virta M. Luminescent bacterial sensor for cadmium and lead. Biosens Bioelectron. 1998;13(9):931–8.
Liao VH, Chien MT, Tseng YY, Ou KL. Assessment of heavy metal bioavailability in contaminated sediments and soils using green fluorescent protein-based bacterial biosensors. Environ Pollut. 2006;142(1):17–23.
Hou Q, Ma A, Wang T, Lin J, Wang H, Du B, et al. Detection of bioavailable cadmium, lead, and arsenic in polluted soil by tailored multiple Escherichia coli whole-cell sensor set. Anal Bioanal Chem. 2015;407(22):6865–71.
Hynninen A, Tonismann K, Virta M. Improving the sensitivity of bacterial bioreporters for heavy metals. Bioeng Bugs. 2010;1(2):132–8.
Branco R, Cristovao A, Morais PV. Highly sensitive, highly specific whole-cell bioreporters for the detection of chromate in environmental samples. PLoS One. 2013;8(1):e54005.
Li PS, Peng ZW, Su J, Tao HC. Construction and optimization of a Pseudomonas putida whole-cell bioreporter for detection of bioavailable copper. Biotechnol Lett. 2014;36(4):761–6.
Tseng HW, Tsai YJ, Yen JH, Chen PH, Yeh YC. A fluorescence-based microbial sensor for the selective detection of gold. Chem Commun (Camb.). 2014;50(14):1735–7.
Cerminati S, Soncini FC, Checa SK. Selective detection of gold using genetically engineered bacterial reporters. Biotechnol Bioeng. 2011;108(11):2553–60.
Wei W, Liu X, Sun P, Wang X, Zhu H, Hong M. Simple whole-cell biodetection and bioremediation of heavy metals based on an engineered lead-specific operon. Environ Sci Technol. 2014;48(6):3363–71.
Bereza-Malcolm L, Aracic S, Franks AE (2016) Development and application of a synthetically-derived lead biosensor construct for use in gram-negative bacteria. Sensors (Basel) 16(12). doi:https://doi.org/10.3390/s16122174.
Fu YJ, Chen WL, Huang QY. Construction of two lux-tagged Hg2+-specific biosensors and their luminescence performance. Appl Microbiol Biotechnol. 2008;79(3):363–70.
Hakkila KM, Nikander PA, Junttila SM, Lamminmaki UJ, Virta MP. Cd-specific mutants of mercury-sensing regulatory protein MerR, generated by directed evolution. Appl Environ Microbiol. 2011;77(17):6215–24.
Cerminati S, Soncini FC, Checa SK. A sensitive whole-cell biosensor for the simultaneous detection of a broad-spectrum of toxic heavy metal ions. Chem Commun (Camb.). 2015;51(27):5917–20.
Tao HC, Peng ZW, Li PS, Yu TA, Su J. Optimizing cadmium and mercury specificity of CadR-based E. coli biosensors by redesign of CadR. Biotechnol Lett. 2013;35(8):1253–8.
Cayron J, Prudent E, Escoffier C, Gueguen E, Mandrand-Berthelot MA, Pignol D, et al. Pushing the limits of nickel detection to nanomolar range using a set of engineered bioluminescent Escherichia coli. Environ Sci Pollut Res Int. 2017;24(1):4–14.
Tibazarwa C, Corbisier P, Mench M, Bossus A, Solda P, Mergeay M (2001)A microbial biosensor to predict bioavailable nickel in soil and its transfer to plants. Environ Pollut 113(1):19–26
Peca L, Kos PB, Mate Z, Farsang A, Vass I. Construction of bioluminescent cyanobacterial reporter strains for detection of nickel, cobalt, and zinc. FEMS Microbiol Lett. 2008;289(2):258–64.
Liu P, Huang Q, Chen W. Construction and application of a zinc-specific biosensor for assessing the immobilization and bioavailability of zinc in different soils. Environ Pollut. 2012;164:66–72.
Gireesh-Babu P, Chaudhari A. Development of a broad-spectrum fluorescent heavy metal bacterial biosensor. Mol Biol Rep. 2012;39(12):11225–9.
Park JN, Sohn MJ, Oh DB, Kwon O, Rhee SK, Hur CG. Identification of the cadmium-inducible Hansenula polymorpha SEO1 gene promoter by transcriptome analysis and its application to whole-cell heavy-metal detection systems. Appl Environ Microbiol. 2007;73(19):5990–6000.
Brown NL, Stoyanov JV, Kidd SP, Hobman JL. The MerR family of transcriptional regulators. FEMS Microbiol Rev. 2003;27(2/3):145–63.
Busenlehner LS, Pennella MA, Giedroc DP. The SmtB/ArsR family of metalloregulatory transcriptional repressors: structural insights into prokaryotic metal resistance. FEMS Microbiol Rev. 2003;27(2/3):131–43.
Pennella MA, Giedroc DP. Structural determinants of metal selectivity in prokaryotic metal-responsive transcriptional regulators. Biometals: an international journal on the role of metal ions in biology, biochemistry, and medicine. 2005;18(4):413–28.
Mitrophanov AY, Groisman EA. Signal integration in bacterial two-component regulatory systems. Genes Dev. 2008;22(19):2601–11.
Tropel D, van der Meer JR. Bacterial transcriptional regulators for degradation pathways of aromatic compounds. Microbiol Mol Biol Rev. 2004;68(3):474–500.
Leonhartsberger S, Huber A, Lottspeich F, Bock A. The hydH/G genes from Escherichia coli code for a zinc and lead responsive two-component regulatory system. J Mol Biol. 2001;307(1):93–105.
Munson GP, Lam DL, Outten FW, O’Halloran TV. Identification of a copper-responsive two-component system on the chromosome of Escherichia coli K-12. J Bacteriol. 2000;182(20):5864–71.
Gupta A, Matsui K, Lo JF, Silver S. Molecular basis for resistance to silver cations in Salmonella. Nat Med. 1999;5(2):183–8.
Dean CR, Poole K. Expression of the ferric enterobactin receptor (PfeA) of Pseudomonas aeruginosa: involvement of a two-component regulatory system. Mol Microbiol. 1993;8(6):1095–103.
Kandegedara A, Thiyagarajan S, Kondapalli KC, Stemmler TL, Rosen BP. Role of bound Zn(II) in the CadC Cd(II)/Pb(II)/Zn(II)-responsive repressor. J Biol Chem. 2009;284(22):14958–65.
Jung J, Jeong H, Kim HJ, Lee DW, Lee SJ. Complete genome sequence of Bacillus oceanisediminis 2691, a reservoir of heavy-metal resistance genes. Mar Genomics. 2016;30:73–6.
Gutierrez JC, Amaro F, Martin-Gonzalez A. Heavy metal whole-cell biosensors using eukaryotic microorganisms: an updated critical review. Front Microbiol. 2015;6:48. https://doi.org/10.3389/fmicb.2015.00048.
Yeliseev AA, Eraso JM, Kaplan S. Differential carotenoid composition of the B875 and B800-850 photosynthetic antenna complexes in Rhodobacter sphaeroides 2.4.1: involvement of spheroidene and spheroidenone in adaptation to changes in light intensity and oxygen availability. J Bacteriol. 1996;178(20):5877–83.
Wang B, Barahona M, Buck M. Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks. Nucleic Acids Res. 2014;42(14):9484–92.
Rong M, He B, McAllister WT, Durbin RK. Promoter specificity determinants of T7 RNA polymerase. Proc Natl Acad Sci USA. 1998;95(2):515–9.
Shis DL, Bennett MR. Library of synthetic transcriptional AND gates built with split T7 RNA polymerase mutants. Proc Natl Acad Sci USA. 2013;110(13):5028–33.
Schaerli Y, Gili M, Isalan M. A split intein T7 RNA polymerase for transcriptional AND-logic. Nucleic Acids Res. 2014;42(19):12322–8.
Pu J, Zinkus-Boltz J, Dickinson BC. Evolution of a split RNA polymerase as a versatile biosensor platform. Nat Chem Biol. 2017;13(4):432–8.
Keenan P, Walmsley RM. The eukaryote alternative:Advantages of using yeasts in place of bacteria in microbial biosensor development. Biotechnol Bioproc Eng. 2000;5(6):387–94.
Shetty RS, Deo SK, Liu Y, Daunert S. Fluorescence-based sensing system for copper using genetically engineered living yeast cells. Biotechnol Bioeng. 2004;88(5):664–70.
Roda A, Roda B, Cevenini L, Michelini E, Mezzanotte L, Reschiglian P. Analytical strategies for improving the robustness and reproducibility of bioluminescent microbial bioreporters. Anal Bioanal Chem. 2011;401(1):201–11.
Juan Carlos Gutiérrez M-G, Díaz S, Amaro F, Ortega R, Gallego A, de Lucas MP. Ciliates as cellular tools to study the eukaryotic cell: heavy metal interactions. Heavy Metal Pollution. New York, NY: Nova Science Publishers; 2008. p. 1–44.
Amaro F, Turkewitz AP, Martin-Gonzalez A, Gutierrez JC. Whole-cell biosensors for detection of heavy metal ions in environmental samples based on metallothionein promoters from Tetrahymena thermophila. Microb Biotechnol. 2011;4(4):513–22.
Diaz S, Amaro F, Rico D, Campos V, Benitez L, Martin-Gonzalez A, et al. Tetrahymena metallothioneins fall into two discrete subfamilies. PLoS One. 2007;2(3):e291.
Gutierrez JC, Amaro F, Diaz S, de Francisco P, Cubas LL, Martin-Gonzalez A. Ciliate metallothioneins: unique microbial eukaryotic heavy metal-binder molecules. J Biol Inorg Chem. 2011;16(7):1025–34.
Kroger S, Law RJ. Biosensors for marine applications. We all need the sea, but does the sea need biosensors? Biosens Bioelectron. 2005;20(10):1903–13.
Shitanda I, Takada K, Sakai Y, Tatsuma T. Amperometric biosensing systems based on motility and gravitaxis of flagellate algae for aquatic risk assessment. Anal Chem. 2005;77(20):6715–8.
Yoshida K, Inoue K, Takahashi Y, Ueda S, Isoda K, Yagi K. Novel carotenoid-based biosensor for simple visual detection of arsenite: characterization and preliminary evaluation for environmental application. Appl Environ Microbiol. 2008;74(21):6730–8.
Brutesco C, Preveral S, Escoffier C, Descamps EC, Prudent E, Cayron J. Bacterial host and reporter gene optimization for genetically encoded whole cell biosensors. Environ Sci Pollut Res Int. 2017;24(1):52–65.
Laddaga RA, Silver S. Cadmium uptake in Escherichia coli K-12. J Bacteriol. 1985;62(3):1100–5.
Jaroslawiecka A, Piotrowska-Seget Z. Lead resistance in micro-organisms. Microbiology. 2014;160(Pt 1):12–25.
Wang B, Barahona M, Buck M. Amplification of small molecule-inducible gene expression via tuning of intracellular receptor densities. Nucleic Acids Res. 2015;43(3):1955–64.
Lim JW, Ha D, Lee J, Lee SK, Kim T. Review of micro/nanotechnologies for microbial biosensors. Front Bioeng Biotechnol. 2015;3:61.
Rothert A, Deo SK, Millner L, Puckett LG, Madou MJ, Daunert S. Whole cell reporter gene-based biosensing systems on a compact disk microfluidics platform. Anal Biochem. 2005;342(1):11–9.
Buffi N, Merulla D, Beutier J, Barbaud F, Beggah S, van Lintel H. Development of a microfluidics biosensor for agarose-bead immobilized Escherichia coli bioreporter cells for arsenite detection in aqueous samples. Lab Chip. 2011;11(14):2369–77.
Kim M, Lim JW, Kim HJ, Lee SK, Lee SJ, Kim T. Chemostat-like microfluidic platform for highly sensitive detection of heavy metal ions using microbial biosensors. Biosens Bioelectron. 2015;65:257–64.
Breitling R, Takano E. Synthetic biology of natural products. Cold Spring Harb Perspect Biol. 2016;8(10)
Lee DW, Lee SJ (2016) Microbial platform cells for synthetic biology. In: Anton Glieder CPK, Diethard Mattanovich, Birgit Wiltschi, Michael Sauer, Eds., pp. 229–254, Synthetic Biology.
Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science. 2007;315(5811):525–8.
Tsai CJ, Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM, Nussinov R. Synonymous mutations and ribosome stalling can lead to altered folding pathways and distinct minima. J Mol Biol. 2008;383(2):281–91.
Bernard E, Wang B. Synthetic cell-based sensors with programmed selectivity and sensitivity. Methods Mol Biol. 2017;1572:349–63.
Wang B, Buck M. Rapid engineering of versatile molecular logic gates using heterologous genetic transcriptional modules. Chem Commun (Camb.). 2014;50(79):11642–4.
Acknowledgements
This work was supported by the Next-Generation BioGreen21 Program (SSAC, PJ01111802), Rural Development Administration, Republic of Korea. This study was also supported by the KRIBB Research Initiative Program and the National Research Foundation of Korea (2015R1A2A2A01005402) funded by the Ministry of Science and ICT, Republic of Korea.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Authors declare that there is no conflict of interest regarding the publication of this article.
Additional information
Published in the topical collection Microbial Biosensors for Analytical Applications with guest editor Gérald Thouand.
Rights and permissions
About this article
Cite this article
Kim, H.J., Jeong, H. & Lee, S.J. Synthetic biology for microbial heavy metal biosensors. Anal Bioanal Chem 410, 1191–1203 (2018). https://doi.org/10.1007/s00216-017-0751-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-017-0751-6