Abstract
S-Adenosylmethionine (SAM) is a crucial small-molecule metabolite widely used in food and medicine. The development of high-throughput biosensors for SAM biosynthesis can significantly improve the titer of SAM. This paper constructed a synthetic transcription factor (TF)-based biosensor for SAM detecting in Saccharomyces cerevisiae. The synthetic TF, named MetJ-hER-VP16, consists of an Escherichia coli-derived DNA-binding domain MetJ, GS linker, the human estrogen receptor binding domain hER, and the viral activation domain VP16. The synthetic biosensor is capable of sensing SAM in a dose-dependent manner with fluorescence as the output. Additionally, it is tightly regulated by the inducer SAM and β-estradiol, which means that the fluorescence output is only available when both are present together. The synthetic SAM biosensor could potentially be applied for high-throughput metabolic engineering and is expected to improve SAM production.
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References
Augustus AM, Reardon PN, Spicer LD (2009) MetJ repressor interactions with DNA probed by in-cell NMR. Proc Natl Acad Sci USA 106(13):5065–5069. https://doi.org/10.1073/pnas.0811130106
Augustus AM, Sage H, Spicer LD (2010) Binding of MetJ repressor to specific and nonspecific DNA and effect of S-adenosylmethionine on these interactions. Biochemistry 49(15):3289–3295. https://doi.org/10.1021/bi902011f
Castano-Cerezo S, Fournie M, Urban P, Faulon J-L, Truan G (2020) Development of a biosensor for detection of benzoic acid derivatives in Saccharomyces cerevisiae. Fron Bioeng Biotechnol 7:372. https://doi.org/10.3389/fbioe.2019.00372
Chen Y, Tan T (2018) Enhanced S-adenosylmethionine production by increasing ATP levels in Baker’s yeast (Saccharomyces cerevisiae). J Agric Food Chem 66(20):5200–5209. https://doi.org/10.1021/acs.jafc.8b00819
Chen Y, Xu D, Fan L, Zhang X, Tan T (2015) Manipulating multi-system of NADPH regulation in Escherichia coli for enhanced S-adenosylmethionine production. RSC Adv 5(51):41103–41111. https://doi.org/10.1039/c5ra02937f
Chen Y, Zhou H, Wang M, Tan T (2017) Control of ATP concentration in Escherichia coli using an ATP-sensing riboswitch for enhanced S-adenosylmethionine production. RSC Adv 7(36):22409–22414. https://doi.org/10.1039/c7ra02538f
Chen J, Liu ZQ, Fang JX, Wang YX, Cao Y, Xu WJ, Wang BJ (2022) A turn-on fluorescence biosensor for sensitive detection of carbaryl using flavourzyme-stabilized gold nanoclusters. Lwt-Food Sci Technol 157:113099. https://doi.org/10.1016/j.lwt
De Berardis D, Orsolini L, Serroni N, Girinelli G, Iasevoli F, Tomasetti C, Di Giannantonio M (2016) A comprehensive review on the efficacy of S-adenosyl-L-methionine in major depressive disorder. CNS Neurol Disord Drug Targets 15(1):35–44. https://doi.org/10.2174/1871527314666150821103825
Deng C, Wu YK, Lv XQ, Li JH, Liu YF, Du GC, Liu L (2022) Refactoring transcription factors for metabolic engineering. Biotechnol Adv 57:107935. https://doi.org/10.1016/j.biotechadv.2022.107935
Feng Y, Xie Z, Jiang X, Li Z, Shen Y, Wang B, Liu J (2018) The applications of promoter-gene-engineered biosensors. Sensors 18(9):2823. https://doi.org/10.3390/s18092823
Feng HB, Yuan YM, Yang Z, Xing XH, Zhang C (2021) Genome-wide genotype-phenotype associations in microbes. J Biosci Bioeng 132(1):1–8. https://doi.org/10.1016/j.jbiosc.2021.03.011
Gibson DG, Young L, Chuang R-Y, Venter JC, Hutchison CA, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6(5):343–345. https://doi.org/10.1038/nmeth.1318
Gietz RD, Schiestl RH (2007) High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat Protoc 2(1):31–34. https://doi.org/10.1038/nprot.2007.13
Gregoire S, Millecamps M, Naso L, Carmo SD, Cuello AC, Szyf M, Stone LS (2016) Therapeutic benefits of the methyl donor S-adenosylmethionine (SAM) on nerve injury-induced mechanical hypersensitivity and cognitive impairment in mice. Pain. https://doi.org/10.1097/j.pain.0000000000000811
Guo T, Chang L, Xiao YS, Liu QY (2015) S-Adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS ONE 10(3):17. https://doi.org/10.1371/journal.pone.0122124
Han LC, Liu XY, Cheng ZY, Cui WJ, Guo JL, Yin J, Zhou ZM (2022) Construction and application of a high-throughput in vivo screening platform for the evolution of nitrile metabolism-related enzymes based on a desensitized repressive biosensor. ACS Synth Biol 11(4):1577–1587. https://doi.org/10.1021/acssynbio.1c00642
Kaczmarek JA, Prather KLJ (2021) Effective use of biosensors for high-throughput library screening for metabolite production. J Ind Microbiol Biotechnol 48(9–10):10. https://doi.org/10.1093/jimb/kuab049
Kanai M, Mizunuma M, Fujii T, Iefuji H (2017) A genetic method to enhance the accumulation of S-adenosylmethionine in yeast. Appl Microbiol Biotechnol 101(4):1351–1357. https://doi.org/10.1007/s00253-017-8098-7
Ke T, Liu J, Zhao S, Wang X, Wang L, Li Y, Hui F (2020) Using Global Transcription Machinery Engineering (GTME) and site-saturation mutagenesis technique to improve ethanol yield of Saccharomyces cerevisiae. Appl Biochem Microbiol 56(5):563–568. https://doi.org/10.1134/s0003683820050087
Li G, Li H, Tan Y, Hao N, Yang X, Chen K, Ouyang P (2020) Improved S-adenosyl-L-methionine production in Saccharomyces cerevisiae using tofu yellow serofluid. J Biotechnol 309:100–106. https://doi.org/10.1016/j.jbiotec.2020.01.004
Liu K, Zhang YS, Liu K, Zhao YQ, Gao B, Tao XY, Wei DZ (2022) De novo design of a transcription factor for a progesterone biosensor. Biosens Bioelectron 203:113897. https://doi.org/10.1016/j.bios.2021.113897
Marti-Arbona R, Teshima M, Anderson PS, Nowak-Lovato KL, Hong-Geller E, Unkefer CJ, Unkefer PJ (2012) Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS. J Mol Microbiol Biotechnol 22(4):205–214. https://doi.org/10.1159/000339717
McIsaac RS, Oakes BL, Wang X, Dummit KA, Botstein D, Noyes MB (2013) Synthetic gene expression perturbation systems with rapid, tunable, single-gene specificity in yeast. Nucleic Acids Res 41(4):10. https://doi.org/10.1093/nar/gks1313
Menegon YA, Gross J, Jacobus AP (2022) How adaptive laboratory evolution can boost yeast tolerance to lignocellulosic hydrolyses. Curr Genet 68:319–342. https://doi.org/10.1007/s00294-022-01237-z
Qin X, Lu J, Zhang Y, Wu X, Qiao X, Wang Z, Qian J (2020) Engineering Pichia pastoris to improve S-adenosyl-l-methionine production using systems metabolic strategies. Biotechnol Bioeng 117(5):1436–1445. https://doi.org/10.1002/bit.27300
Qiu C, Zhai H, Hou J (2019) Biosensors design in yeast and applications in metabolic engineering. Fems Yeast Res 19(8):82. https://doi.org/10.1093/femsyr/foz082
Qiu X, Xu P, Zhao X, Du G, Li J (2020) Combining genetically-encoded biosensors with high throughput strain screening to maximize erythritol production in Yarrowia lipolytica. Metab Eng 60:66–76. https://doi.org/10.1016/j.ymben.2020.03.006
Ruan LY, Li L, Zou D, Jiang C, Wen ZY, Chen SW, Wei XT (2019) Metabolic engineering of Bacillus amyloliquefaciens for enhanced production of S-adenosylmethionine by coupling of an engineered S-adenosylmethionine pathway and the tricarboxylic acid cycle. Biotechnol Biofuels 12(1):12. https://doi.org/10.1186/s13068-019-1554-0
Si T, Chao R, Min YH, Wu YY, Ren W, Zhao HM (2017) Automated multiplex genome-scale engineering in yeast. Nat Commun 8:12. https://doi.org/10.1038/ncomms15187
Silveri MM, Parow AM, Villafuerte RA, Damico KE, Goren J, Stoll AL, Renshaw PF (2003) S-Adenosyl-l-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects. Biol Psychiat 54(8):833–839. https://doi.org/10.1016/s0006-3223(03)00064-7
Sun H, Zhao H, Ang EL (2020) A new biosensor for stilbenes and a cannabinoid enabled by genome mining of a transcriptional regulator. ACS Synth Biol 9(4):698–705. https://doi.org/10.1021/acssynbio.9b00443
Umeyama T, Okada S, Ito T (2013) Synthetic gene circuit-mediated monitoring of endogenous metabolites: identification of GAL11 as a novel multicopy enhancer of S-adenosylmethionine level in yeast. ACS Synth Biol 2(8):425–430. https://doi.org/10.1021/sb300115n
Wan X, Marsafari M, Xu P (2019) Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives. Microb Cell Fact 18:61. https://doi.org/10.1186/s12934-019-1111-3
Wang RF, Cress BF, Yang Z, Hordines JC, Zhao SJ, Jung GY, Koffas MAG (2019) Design and characterization of biosensors for the screening of modular assembled naringenin biosynthetic library in Saccharomyces cerevisiae. ACS Synth Biol 8(9):2121–2130. https://doi.org/10.1021/acssynbio.9b00212
Wang GK, Ozmerih S, Guerreiro R, Meireles AC, Carolas A, Milne N, Borodina I (2020) Improvement of cis, cis-muconic acid production in Saccharomyces cerevisiae through biosensor-aided genome engineering. ACS Synth Biol 9(3):634–646. https://doi.org/10.1021/acssynbio.9b00477
Yan GB, Li X, Yang J, Li ZC, Hou J, Rao B, Wang YP (2021) Cost-effective production of ATP and S-adenosylmethionine using engineered multidomain scaffold proteins. Biomolecules 11(11):15. https://doi.org/10.3390/biom11111706
Zadran S, Sanchez D, Zadran H, Amighi A, Otiniano E, Wong K (2013) Enhanced-acceptor fluorescence-based single cell ATP biosensor monitors ATP in heterogeneous cancer populations in real time. Biotech Lett 35(2):175–180. https://doi.org/10.1007/s10529-012-1065-6
Zhang Y, Shi S (2021) Transcription factor-based biosensor for dynamic control in yeast for natural product synthesis. Front Bioeng Biotechnol 10:911–922. https://doi.org/10.3389/fbioe.2021.635265
Acknowledgements
This work was supported by the young backbone teachers funding project of Henan Province (2021GGJS047) the Students Research and Training Program (SRTP) of Henan University of Science and Technology (2022189).
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Chen, Y., Zheng, H., Yang, j. et al. Development of a synthetic transcription factor-based S-adenosylmethionine biosensor in Saccharomyces cerevisiae. Biotechnol Lett 45, 255–262 (2023). https://doi.org/10.1007/s10529-022-03338-8
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DOI: https://doi.org/10.1007/s10529-022-03338-8