Abstract
Analyte detection is a major component of fieldwork, environmental surveillance, and health protection, but lack of resources or access to instruments can create challenges in technology-limited environments such as remote research sites or low- and middle-income countries (LMICs). Whole-cell yeast-based biosensors provide potential solutions to these barriers. Here, we discuss the components of whole-cell yeast-based biosensors, emphasizing the process by which they are designed for their analyte of interest, approaches for harnessing them to function in particular research environments, and their advantages and disadvantages relative to other analytical tools. We provide examples of the various purposes for which existing whole-cell yeast-based biosensors have been used, focusing most on those appropriate for detecting externally-generated analytes in technology-limited settings. The further development of field-friendly whole-cell yeast-based biosensors still faces challenges, including the need to reduce the time from contact with the analyte to signal readout of the biosensor. Regardless, the inexpensive, robust, portable, environmentally friendly, and highly modular nature of yeast-based biosensors suggests that they could become useful tools for a range of analytical tasks.
Heather A.M. Shepherd and Emilia-Maria A. Bondarenko are Co-first authors.
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References
Adachi T, Nakamura Y (2019) Aptamers: a review of their chemical properties and modifications for therapeutic application. Molecules 23:4229. https://doi.org/10.3390/molecules24234229
Adeniran A, Sherer M, Tyo KEJ (2015) Yeast-based biosensors: design and applications. FEMS Yeast Res 15:1–15. https://doi.org/10.1111/1567-1364.12203
Adeniran A, Stainbrook S, Bostick JW, Tyo KEJ (2018) Correction to “Detection of a peptide biomarker by engineered yeast receptors.” ACS Synth Biol 7:1973–1973. https://doi.org/10.1021/acssynbio.8b00291
Ahmad R, Dalziel JE (2020) G protein-coupled receptors in taste physiology and pharmacology. Front Pharmacol 11:587664. https://doi.org/10.3389/fphar.2020.587664
Allard STM (2008) Bioluminescent reporter genes. https://www.promega.com/resources/pubhub/enotes/bioluminescent-reporter-genes/
Aranda-Díaz A, Mace K, Zuleta I et al (2017) Robust synthetic circuits for two-dimensional control of gene expression in yeast. ACS Synth Biol 6:545–554. https://doi.org/10.1021/acssynbio.6b00251
Ballard ZS, Joung H-A, Goncharov A et al (2020) Deep learning-enabled point-of-care sensing using multiplexed paper-based sensors. NPJ Digital Medicine 3:1–8. https://doi.org/10.1038/s41746-020-0274-y
Baron U, Bujard H (2000) Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. Methods Enzymol 327:401–421. https://doi.org/10.1016/s0076-6879(00)27292-3
Berg B, Cortazar B, Tseng D et al (2015) Cell phone-based hand-held microplate reader for point-of-care testing of enzyme-linked immunosorbent assays. ACS Nano 9:7857–7866. https://doi.org/10.1021/acsnano.5b03203
Billinton N, Barker MG, Michel CE et al (1998) Development of a green fluorescent protein reporter for a yeast genotoxicity biosensor. Biosens Bioelectron 13:831–838. https://doi.org/10.1016/s0956-5663(98)00049-9
Bittner M, Jarque S, Hilscherová K (2015) Polymer-immobilized ready-to-use recombinant yeast assays for the detection of endocrine disruptive compounds. Chemosphere 132:56–62. https://doi.org/10.1016/j.chemosphere.2015.02.063
Borse V, Patil AS, Srivastava R (2017) Development and testing of portable fluorescence reader (PorFloRTM). In: 2017 9th international conference on communication systems and networks (COMSNETS). pp 498–501
Bui VN, Nguyen TTH, Bettarel Y et al (2015) Genotoxicity of chemical compounds identification and assessment by yeast cells transformed with GFP reporter constructs regulated by the PLM2 or DIN7 promoter. Int J Toxicol 34:31–43. https://doi.org/10.1177/1091581814566870
Burrill DR, Silver PA (2011) Synthetic circuit identifies subpopulations with sustained memory of DNA damage. Genes Dev 25:434–439. https://doi.org/10.1101/gad.1994911
Cevenini L, Lopreside A, Calabretta MM et al (2018) A novel bioluminescent NanoLuc yeast-estrogen screen biosensor (nanoYES) with a compact wireless camera for effect-based detection of endocrine-disrupting chemicals. Anal Bioanal Chem 410:1237–1246. https://doi.org/10.1007/s00216-017-0661-7
Chen B, Lee HL, Heng YC et al (2018) Synthetic biology toolkits and applications in Saccharomyces cerevisiae. Biotechnol Adv 36:1870–1881. https://doi.org/10.1016/j.biotechadv.2018.07.005
Conroy PJ, Hearty S, Leonard P, O’Kennedy RJ (2009) Antibody production, design and use for biosensor-based applications. Semin Cell Dev Biol 20:10–26. https://doi.org/10.1016/j.semcdb.2009.01.010
Dai B, Wang L, Wang Y et al (2018) Single-cell nanometric coating towards whole-cell-based biodevices and biosensors. ChemistrySelect 3:7208–7221. https://doi.org/10.1002/slct.201800963
Dameron CT, Winge DR, George GN et al (1991) A copper-thiolate polynuclear cluster in the ACE1 transcription factor. PNAS 88:6127–6131. https://doi.org/10.1073/pnas.88.14.6127
Emr SD, Schauer I, Hansen W et al (1984) Invertase beta-galactosidase hybrid proteins fail to be transported from the endoplasmic reticulum in Saccharomyces cerevisiae. Mol Cell Biol 4:2347–2355. https://doi.org/10.1128/MCB.4.11.2347
Fine T, Leskinen P, Isobe T et al (2006) Luminescent yeast cells entrapped in hydrogels for estrogenic endocrine disrupting chemical biodetection. Biosens Bioelectron 21:2263–2269. https://doi.org/10.1016/j.bios.2005.11.004
Fuentes N, Silveyra P (2019) Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol 116:135–170. https://doi.org/10.1016/bs.apcsb.2019.01.001
Gao CY, Pinkham JL (2000) Tightly regulated, β-estradiol dose-dependent expression system for yeast. Biotechniques 29:1226–1231. https://doi.org/10.2144/00296st02
Gardner JM, Jaspersen SL (2014) Manipulating the yeast genome: deletion, mutation, and tagging by PCR. Methods Mol Biol 1205:45–78. https://doi.org/10.1007/978-1-4939-1363-3_5
Gnügge R, Rudolf F (2017) Saccharomyces cerevisiae shuttle vectors. Yeast 34:205–221. https://doi.org/10.1002/yea.3228
Gong L, Yang G, Yang B, Gu J (2020) Development of the yeast Saccharomyces cerevisiae as a biosensor for the toxicity detection of toxic substances. bioRxiv 07 Jan 2020. 898106. https://doi.org/10.1101/2020.01.07.898106
Grewal PS, Modavi C, Russ ZN et al (2018) Bioproduction of a betalain color palette in Saccharomyces cerevisiae. Metab Eng 45:180–188. https://doi.org/10.1016/j.ymben.2017.12.008
Gruber CJ, Gruber DM, Gruber IML et al (2004) Anatomy of the estrogen response element. Trends Endocrinol Metab 15:73–78. https://doi.org/10.1016/j.tem.2004.01.008
Hartner FS, Glieder A (2006) Regulation of methanol utilisation pathway genes in yeasts. Microb Cell Fact 5:39. https://doi.org/10.1186/1475-2859-5-39
Herkommerová K, Zemančíková J, Sychrová H, Antošová Z (2018) Immobilization in polyvinyl alcohol hydrogel enhances yeast storage stability and reusability of recombinant laccase-producing S. cerevisiae. Biotechnol Lett 40:405–411. https://doi.org/10.1007/s10529-017-2485-0
Hilger D, Masureel M, Kobilka BK (2018) Structure and dynamics of GPCR signaling complexes. Nat Struct Mol Biol 25:4–12. https://doi.org/10.1038/s41594-017-0011-7
Hollis RP, Killham K, Glover LA (2000) Design and application of a biosensor for monitoring toxicity of compounds to eukaryotes. Appl Environ Microbiol 66:1676–1679
Hori K, Sen A, Artavanis-Tsakonas S (2013) Notch signaling at a glance. J Cell Sci 126:2135–2140. https://doi.org/10.1242/jcs.127308
Hung C-W, Martínez-Márquez JY, Javed FT, Duncan MC (2018) A simple and inexpensive quantitative technique for determining chemical sensitivity in Saccharomyces cerevisiae. Sci Rep 8:11919. https://doi.org/10.1038/s41598-018-30305-z
Ito-Harashima S, Matano M, Onishi K et al (2020) Construction of reporter gene assays using CWP and PDR mutant yeasts for enhanced detection of various sex steroids. Genes Environ 42:20. https://doi.org/10.1186/s41021-020-00159-x
Jarque S, Bittner M, Hilscherová K (2016) Freeze-drying as suitable method to achieve ready-to-use yeast biosensors for androgenic and estrogenic compounds. Chemosphere 148:204–210. https://doi.org/10.1016/j.chemosphere.2016.01.038
Jarque S, Bittner M, Blaha L, Hilscherova K (2016) Yeast biosensors for detection of environmental pollutants: current state and limitations. Trends Biotechnol 34:408–419. https://doi.org/10.1016/j.tibtech.2016.01.007
Jeyaprakash A, Welch JW, Fogel S (1991) Multicopy CUP1 plasmids enhance cadmium and copper resistance levels in yeast. Mol Gen Genet 225:363–368. https://doi.org/10.1007/BF00261675
Klauser B, Atanasov J, Siewert LK, Hartig JS (2015) Ribozyme-based aminoglycoside switches of gene expression engineered by genetic selection in S. cerevisiae. ACS Synth Biol 4:516–525. https://doi.org/10.1021/sb500062p
Lehmann M, Riedel K, Adler K, Kunze G (2000) Amperometric measurement of copper ions with a deputy substrate using a novel Saccharomyces cerevisiae sensor. Biosens Bioelectron 15:211–219. https://doi.org/10.1016/S0956-5663(00)00060-9
Lengger B, Jensen MK (2020) Engineering G protein-coupled receptor signalling in yeast for biotechnological and medical purposes. FEMS Yeast Res 20. https://doi.org/10.1093/femsyr/foz087
Leskinen P, Virta M, Karp M (2003) One-step measurement of firefly luciferase activity in yeast. Yeast 20:1109–1113. https://doi.org/10.1002/yea.1024
Lei Y, Chen W, Mulchandani A (2006) Microbial biosensors. Analytica Chimica Acta 568(1):200–210. https://doi.org/10.1016/j.aca.2005.11.065
Louvion JF, Havaux-Copf B, Picard D (1993) Fusion of GAL4-VP16 to a steroid-binding domain provides a tool for gratuitous induction of galactose-responsive genes in yeast. Gene 131:129–134. https://doi.org/10.1016/0378-1119(93)90681-r
Lu Y, Tian Y, Wang R et al (2015) Dual fluorescent protein-based bioassay system for the detection of genotoxic chemical substances in Saccharomyces cerevisiae. Toxicol Mech Methods 25:698–707. https://doi.org/10.3109/15376516.2015.1070305
Malcı K, Walls LE, Rios-Solis L (2020) Multiplex genome engineering methods for yeast cell factory development. Front Bioeng Biotechnol 8:1264. https://doi.org/10.3389/fbioe.2020.589468
Martin-Yken H (2020) Yeast-based biosensors: current applications and new developments. Biosensors 10:51. https://doi.org/10.3390/bios10050051
Miller RA, Brown G, Barron E et al (2020a) Development of a paper-immobilized yeast biosensor for the detection of physiological concentrations of doxycycline in technology-limited settings. Anal Methods 12:2123–2132. https://doi.org/10.1039/D0AY00001A
Miller RA, Lee S, Fridmanski EJ et al (2020b) “Scentsor”: a whole-cell yeast biosensor with an olfactory reporter for low-cost and equipment-free detection of pharmaceuticals. ACS Sensors 5:3025–3030. https://doi.org/10.1021/acssensors.0c01344
Möckli N, Auerbach D (2004) Quantitative β-galactosidase assay suitable for high-throughput applications in the yeast two-hybrid system. Biotechniques 36:872–876. https://doi.org/10.2144/04365PT03
Mukherjee K, Bhattacharyya S, Peralta-Yahya P (2015) GPCR-based chemical biosensors for medium-chain fatty acids. ACS Synth Biol 4:1261–1269. https://doi.org/10.1021/sb500365m
Nakamura Y, Hashimoto T, Ishii J, Kondo A (2016) Dual-color reporter switching system to discern dimer formations of G-protein-coupled receptors using Cre/loxP site-specific recombination in yeast. Biotechnol Bioeng 113:2178–2190. https://doi.org/10.1002/bit.25974
Nelson DL, Cox MM (2017) Lehninger principles of biochemistry. In: Freeman WH, 7th edn. New York, NY
Ong JY, Pence JT, Molik DC et al (2021) Yeast grown in continuous culture systems can detect mutagens with improved sensitivity relative to the Ames test. PLoS ONE 16:e0235303. https://doi.org/10.1371/journal.pone.0235303
Ostrov N, Jimenez M, Billerbeck S et al (2017) A modular yeast biosensor for low-cost point-of-care pathogen detection. Sci Adv 3:e1603221. https://doi.org/10.1126/sciadv.1603221
Paetkau DW, Riese JA, MacMorran WS et al (1994) Interaction of the yeast RAD7 and SIR3 proteins: implications for DNA repair and chromatin structure. Genes Dev 8:2035–2045. https://doi.org/10.1101/gad.8.17.2035
Peltomaa R, Benito-Peña E, Barderas R, Moreno-Bondi MC (2019) Phage display in the quest for new selective recognition elements for biosensors. ACS Omega 4:11569–11580. https://doi.org/10.1021/acsomega.9b01206
Ponamoreva ON, Kamanina OA, Alferov VA et al (2015) Yeast-based self-organized hybrid bio-silica sol–gels for the design of biosensors. Biosens Bioelectron 67:321–326. https://doi.org/10.1016/j.bios.2014.08.045
Redden H, Morse N, Alper HS (2015) The synthetic biology toolbox for tuning gene expression in yeast. FEMS Yeast Res 15:1–10. https://doi.org/10.1111/1567-1364.12188
Renneberg T, Kwan RCH, Chan C et al (2004) A salt-tolerant yeast-based microbial sensor for 24 hour community wastewater monitoring in coastal regions. Microchim Acta 148:235–240. https://doi.org/10.1007/s00604-004-0266-7
Roney IJ, Rudner AD, Couture J-F, Kærn M (2016) Improvement of the reverse tetracycline transactivator by single amino acid substitutions that reduce leaky target gene expression to undetectable levels. Sci Rep 6:27697. https://doi.org/10.1038/srep27697
Routledge EJ, Sumpter JP (1996) Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen. Environ Toxicol Chem 15:241–248. https://doi.org/10.1002/etc.5620150303
Routledge SJ, Mikaliunaite L, Patel A et al (2016) The synthesis of recombinant membrane proteins in yeast for structural studies. Methods 95:26–37. https://doi.org/10.1016/j.ymeth.2015.09.027
Schindler D (2020) Genetic engineering and synthetic genomics in yeast to understand life and boost biotechnology. Bioengineering 7:137. https://doi.org/10.3390/bioengineering7040137
Seo KS, Choo KH, Chang HN, Park JK (2009) A flow injection analysis system with encapsulated high-density Saccharomyces cerevisiae cells for rapid determination of biochemical oxygen demand. Appl Microbiol Biotechnol 83:217–223. https://doi.org/10.1007/s00253-008-1852-0
Shaw WM, Yamauchi H, Mead J et al (2019) Engineering a model cell for rational tuning of GPCR signaling. Cell 177:782-796.e27. https://doi.org/10.1016/j.cell.2019.02.023
Shepherd HAM, Trentman MT, Tank JL, et al (2021) Development of a yeast-based assay for bioavailable phosphorous. bioRxiv 28 Feb 2021. 433264. https://doi.org/10.1101/2021.02.28.433264
Smith DF, Toft DO (1993) Steroid receptors and their associated proteins. Mol Endocrinol 7:4–11. https://doi.org/10.1210/mend.7.1.8446107
Smith AD, Logeman BL, Thiele DJ (2017) Copper acquisition and utilization in fungi. Annu Rev Microbiol 71:597–623. https://doi.org/10.1146/annurev-micro-030117-020444
Stainbrook SC, Yu JS, Reddick MP et al (2017) Modulating and evaluating receptor promiscuity through directed evolution and modeling. Protein Eng Des Sel 30:455–465. https://doi.org/10.1093/protein/gzx018
Tamai KT, Liu X, Silar P et al (1994) Heat shock transcription factor activates yeast metallothionein gene expression in response to heat and glucose starvation via distinct signalling pathways. Mol Cell Biol 14:8155–8165
Tag K, Riedel K, Bauer H-J, Hanke G, Baronian KHR, Kunze G (2007) Amperometric detection of Cu2+ by yeast biosensors using flow injection analysis (FIA). Sensors and Actuators B: Chemical 122(2):403–409. https://doi.org/10.1016/j.snb.2006.06.007
Trentman MT, Tank JL, Shepherd HAM, et al (2021) Characterizing bioavailable phosphorus concentrations in an agricultural stream during hydrologic and streambed disturbances. Biogeochemistry. https://doi.org/10.1007/s10533-021-00803-w
Urlinger S, Baron U, Thellmann M et al (2000) Exploring the sequence space for tetracycline-dependent transcriptional activators: novel mutations yield expanded range and sensitivity. PNAS 97:7963–7968. https://doi.org/10.1073/pnas.130192197
Van Wyk N, Kroukamp H, Pretorius IS (2018) The smell of synthetic biology: engineering strategies for aroma compound production in yeast. Fermentation 4:54. https://doi.org/10.3390/fermentation4030054
Vashist SK, Mudanyali O, Schneider EM et al (2014) Cellphone-based devices for bioanalytical sciences. Anal Bioanal Chem 406:3263–3277. https://doi.org/10.1007/s00216-013-7473-1
Venkatesh AG, Sun A, Brickner H et al (2015) Yeast dual-affinity biobricks: progress towards renewable whole-cell biosensors. Biosens Bioelectron 70:462–468. https://doi.org/10.1016/j.bios.2015.03.044
Versele M, Lemaire K, Thevelein JM (2001) Sex and sugar in yeast: two distinct GPCR systems. EMBO Rep 2:574–579. https://doi.org/10.1093/embo-reports/kve132
Vieira Gomes AM, Souza Carmo T, Silva Carvalho L, et al (2018) Comparison of yeasts as hosts for recombinant protein production. Microorganisms 6:38. https://doi.org/10.3390/microorganisms6020038
Vopálenská I, Váchová L, Palková Z (2015) New biosensor for detection of copper ions in water based on immobilized genetically modified yeast cells. Biosens Bioelectron 72:160–167. https://doi.org/10.1016/j.bios.2015.05.006
Wang L-J, Naudé N, Demissie M et al (2018) Analytical validation of an ultra low-cost mobile phone microplate reader for infectious disease testing. Clin Chim Acta 482:21–26. https://doi.org/10.1016/j.cca.2018.03.013
Wang J, Yang D, Guo X et al (2020) A novel RNA aptamer-modified riboswitch as chemical sensor. Anal Chim Acta 1100:240–249. https://doi.org/10.1016/j.aca.2019.11.071
Weaver AA, Halweg S, Joyce M et al (2015) Incorporating yeast biosensors into paper-based analytical tools for pharmaceutical analysis. Anal Bioanal Chem 407:615–619. https://doi.org/10.1007/s00216-014-8280-z
Wei Q, Qi H, Luo W et al (2013) Fluorescent imaging of single nanoparticles and viruses on a smart phone. ACS Nano 7:9147–9155. https://doi.org/10.1021/nn4037706
Yoon HK, Jung ST, Kim J-H, Yoo TH (2012) Recent development of highly sensitive protease assay methods: signal amplification through enzyme cascades. Biotechnol Bioproc E 17:1113–1119. https://doi.org/10.1007/s12257-012-0545-9
Yu D, Liao L, Zhang J et al (2018) A novel, easy and rapid method for constructing yeast two-hybrid vectors using in-fusion technology. Biotechniques 64:219–224. https://doi.org/10.2144/btn-2018-0007
Yudina NY, Arlyapov VA, Chepurnova MA et al (2015) A yeast co-culture-based biosensor for determination of waste water contamination levels. Enzyme Microb Technol 78:46–53. https://doi.org/10.1016/j.enzmictec.2015.06.008
Zhang CC, Glenn KA, Kuntz MA, Shapiro DJ (2000) High level expression of full-length estrogen receptor in Escherichia coli is facilitated by the uncoupler of oxidative phosphorylation, CCCP. J Steroid Biochem Mol Biol 74:169–178. https://doi.org/10.1016/s0960-0760(00)00120-5
Zhang J, Jensen MK, Keasling JD (2015) Development of biosensors and their application in metabolic engineering. Curr Opin Chem Biol 28:1–8. https://doi.org/10.1016/j.cbpa.2015.05.013
Zhao H, Zhang Y, Pan M et al (2019) Dynamic imaging of cellular pH and redox homeostasis with a genetically encoded dual-functional biosensor, pHaROS, in yeast. J Biol Chem 294:15768–15780. https://doi.org/10.1074/jbc.RA119.007557
Zhou X, Vink M, Klaver B et al (2006) Optimization of the Tet-On system for regulated gene expression through viral evolution. Gene Ther 13:1382–1390. https://doi.org/10.1038/sj.gt.3302780
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Shepherd, H.A.M., Bondarenko, EM.A., Jennings, K.M., Miller, R.A., Goodson, H.V. (2022). Whole Cell Yeast-Based Biosensors. In: Darvishi Harzevili, F. (eds) Synthetic Biology of Yeasts. Springer, Cham. https://doi.org/10.1007/978-3-030-89680-5_4
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