簡易檢索 / 詳目顯示

研究生: 劉建平
Liu, Jian-Pin
論文名稱: 優化全細胞生物感測器對苯丙胺酸與食品檢測之應用
Genetic Engineering to Optimize Whole-cell Biosensor Toward Phenylalanine for Food Determination applications
指導教授: 葉怡均
Yeh, Yi-Chun
口試委員: 杜玲嫻
Tu, Ling-Hsien
蔡伸隆
Tsai, Shen-Long
葉怡均
Yeh, Yi-Chun
口試日期: 2022/07/05
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 121
中文關鍵詞: 苯丙酮尿症全細胞生物感測器苯丙胺酸食品檢測
英文關鍵詞: phenylketonuria (PKU), whole-cell biosensor, phenylalanine (Phe), food analysis, soft drinks
DOI URL: http://doi.org/10.6345/NTNU202200974
論文種類: 學術論文
相關次數: 點閱:102下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 中文摘要 i ABSTRACT ii 縮寫表 iii 目錄 v 圖目錄 ix 表目錄 xiii Chapter 1緒論 1 1-1全細胞生物感測器 (Whole-cell biosensor) 1 1-1-1生物感測器 1 1-1-2 大腸桿菌 2 1-1-3 熱誘導 4 1-2 芳香族胺基酸調控 5 1-2-1 芳香族胺基酸在大腸桿菌體內合成路徑 5 1-2-2 TyrR regulon 7 1-2-3 Activation 10 1-2-4 Repression 11 1-3 苯丙酮尿症 (Phenylketonuria) 13 1-3-1 胺基酸代謝疾病 13 1-3-2 苯丙酮尿症 13 1-3-3 治療方法 15 1-3-4 檢測方法回顧 17 1-4 苯乙胺代謝與其衍伸藥物檢測 21 1-4-1 苯乙胺代謝途徑 21 1-4-2 苯乙胺衍伸藥物-安非他命 22 1-4-3 檢測方法 25 1-5 實驗動機與目的 30 Chapter 2 實驗方法與設計 32 2-1 實驗儀器 32 2-2 實驗藥品 34 2-3 基因工程 38 2-3-1 畫盤 (Plate streaking) 38 2-3-2 抽取質體 (Plasmid extraction) 39 2-3-3 聚合酶鏈鎖反應 (Polymerase Chain Reaction, PCR) 39 2-3-4 膠體電泳 (Gel electrophoresis)與膠體萃取 (Gel extraction) 41 2-3-5 限制酶切割 (restriction enzyme digestion) 42 2-3-6 接合 (Ligation) 43 2-3-7 Golden Gate Assembly 44 2-3-8 突變 (Mutagenesis) 46 2-3-9 轉形作用 (transformation) 47 2-3-10 質體檢查 (PCR check) 48 2-3-11 定序 (Sequencing) 49 2-3-12 存菌 (Glycerol stock) 49 2-3-13 雙質體系統建構 49 2-4 苯丙酮尿症生物感測器設計與實驗方法 50 2-4-1 啟動子設計 50 2-4-2 培養過程 51 2-4-3 誘導試劑 51 2-4-4 螢光分析定量 52 2-4-5 真實樣品前處理 52 2-4-6 真實樣品培養條件 54 2-4-7 數據處理 55 2-5 苯乙胺衍生藥物感測器開發 55 2-5-1 質體設計 55 2-5-2 突變條件 55 2-5-3 培養條件 57 Chapter 3 實驗結果與討論 58 3-1 苯丙胺酸感測器 58 3-1-1 PtyrP啟動子突變 58 3-1-2 TyrR蛋白優化 60 3-1-3 PRPL 啟動子系統 63 3-1-5 IPTG誘導濃度優化 65 3-1-6雙訊號系統優化 66 3-1-7 mTCG質體優化 69 3-1-8 雙質體系統設計與比較 70 3-1-9 誘導時間優化 72 3-1-10 雙質體系統與單質體系統的比較 75 3-1-11 真實樣品測試 79 3-2 苯乙胺感測器 83 3-3 苯乙胺衍伸物感測器開發 85 3-3-1 培養條件優化與感測器選擇 85 3-3-2 buffer termination 建構 87 3-3-3 抗抗生素質體建構 89 Chapter 4 結論 92 附錄 94 附錄1 菌種 94 附錄2 質體 102 附錄3 引子 112 Reference 115

    1. Ziegler, C.; Gopel, W., Biosensor development. Curr Opin Chem Biol 1998, 2 (5), 585-91.
    2. Gu, M. B.; Mitchell, R. J.; Kim, B. C., Whole-cell-based biosensors for environmental biomonitoring and application. Adv Biochem Eng Biotechnol 2004, 87, 269-305.
    3. Tenaillon, O.; Skurnik, D.; Picard, B.; Denamur, E., The population genetics of commensal Escherichia coli. Nat Rev Microbiol 2010, 8 (3), 207-17.
    4. Nataro, J. P.; Kaper, J. B., Diarrheagenic Escherichia coli. Clin Microbiol Rev 1998, 11 (1), 142-201.
    5. Erlich, H. A.; Gelfand, D.; Sninsky, J. J., Recent advances in the polymerase chain reaction. Science 1991, 252 (5013), 1643-51.
    6. Anton, B. P.; Raleigh, E. A., Complete Genome Sequence of NEB 5-alpha, a Derivative of Escherichia coli K-12 DH5alpha. Genome Announc 2016, 4 (6).
    7. Jeong, H.; Barbe, V.; Lee, C. H.; Vallenet, D.; Yu, D. S.; Choi, S. H.; Couloux, A.; Lee, S. W.; Yoon, S. H.; Cattolico, L.; Hur, C. G.; Park, H. S.; Segurens, B.; Kim, S. C.; Oh, T. K.; Lenski, R. E.; Studier, F. W.; Daegelen, P.; Kim, J. F., Genome sequences of Escherichia coli B strains REL606 and BL21(DE3). J Mol Biol 2009, 394 (4), 644-52.
    8. Dumon-Seignovert, L.; Cariot, G.; Vuillard, L., The toxicity of recombinant proteins in Escherichia coli: a comparison of overexpression in BL21(DE3), C41(DE3), and C43(DE3). Protein Expr Purif 2004, 37 (1), 203-6.
    9. Durfee, T.; Nelson, R.; Baldwin, S.; Plunkett, G., 3rd; Burland, V.; Mau, B.; Petrosino, J. F.; Qin, X.; Muzny, D. M.; Ayele, M.; Gibbs, R. A.; Csorgo, B.; Posfai, G.; Weinstock, G. M.; Blattner, F. R., The complete genome sequence of Escherichia coli DH10B: insights into the biology of a laboratory workhorse. J Bacteriol 2008, 190 (7), 2597-606.
    10. Cosgriff, A. J.; Brasier, G.; Pi, J.; Dogovski, C.; Sarsero, J. P.; Pittard, A. J., A study of AroP-PheP chimeric proteins and identification of a residue involved in tryptophan transport. J Bacteriol 2000, 182 (8), 2207-17.
    11. Isabella, V. M.; Ha, B. N.; Castillo, M. J.; Lubkowicz, D. J.; Rowe, S. E.; Millet, Y. A.; Anderson, C. L.; Li, N.; Fisher, A. B.; West, K. A.; Reeder, P. J.; Momin, M. M.; Bergeron, C. G.; Guilmain, S. E.; Miller, P. F.; Kurtz, C. B.; Falb, D., Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. Nat Biotechnol 2018, 36 (9), 857-864.
    12. Charbonneau, M. R.; Denney, W. S.; Horvath, N. G.; Cantarella, P.; Castillo, M. J.; Puurunen, M. K.; Brennan, A. M., Development of a mechanistic model to predict synthetic biotic activity in healthy volunteers and patients with phenylketonuria. Commun Biol 2021, 4 (1), 898.
    13. Brunner, M.; Bujard, H., Promoter recognition and promoter strength in the Escherichia coli system. EMBO J 1987, 6 (10), 3139-44.
    14. Monchy, S.; Benotmane, M. A.; Wattiez, R.; van Aelst, S.; Auquier, V.; Borremans, B.; Mergeay, M.; Taghavi, S.; van der Lelie, D.; Vallaeys, T., Transcriptomic and proteomic analyses of the pMOL30-encoded copper resistance in Cupriavidus metallidurans strain CH34. Microbiology (Reading) 2006, 152 (Pt 6), 1765-1776.
    15. Chee, W. K. D.; Yeoh, J. W.; Dao, V. L.; Poh, C. L., Highly Reversible Tunable Thermal-Repressible Split-T7 RNA Polymerases (Thermal-T7RNAPs) for Dynamic Gene Regulation. ACS Synth Biol 2022, 11 (2), 921-937.
    16. Kortmann, J.; Narberhaus, F., Bacterial RNA thermometers: molecular zippers and switches. Nat Rev Microbiol 2012, 10 (4), 255-65.
    17. Zheng, Y.; Meng, F.; Zhu, Z.; Wei, W.; Sun, Z.; Chen, J.; Yu, B.; Lou, C.; Chen, G. Q., A tight cold-inducible switch built by coupling thermosensitive transcriptional and proteolytic regulatory parts. Nucleic Acids Res 2019, 47 (21), e137.
    18. Harder, B. J.; Bettenbrock, K.; Klamt, S., Temperature-dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli. Biotechnol Bioeng 2018, 115 (1), 156-164.
    19. Valdez-Cruz, N. A.; Caspeta, L.; Perez, N. O.; Ramirez, O. T.; Trujillo-Roldan, M. A., Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters. Microb Cell Fact 2010, 9, 18.
    20. Polen, T.; Kramer, M.; Bongaerts, J.; Wubbolts, M.; Wendisch, V. F., The global gene expression response of Escherichia coli to L-phenylalanine. J Biotechnol 2005, 115 (3), 221-37.
    21. Pittard, J.; Camakaris, H.; Yang, J., The TyrR regulon. Mol Microbiol 2005, 55 (1), 16-26.
    22. Andrews, A. E.; Dickson, B.; Lawley, B.; Cobbett, C.; Pittard, A. J., Importance of the position of TYR R boxes for repression and activation of the tyrP and aroF genes in Escherichia coli. J Bacteriol 1991, 173 (16), 5079-85.
    23. Rampini, S.; Vollmin, J. A.; Bosshard, H. R.; Muller, M.; Curtius, H. C., Aromatic acids in urine of healthy infants, persistent hyperphenylalaninemia, and phenylketonuria, before and after phenylalanine load. Pediatr Res 1974, 8 (7), 704-9.
    24. Swarna, M.; Jyothy, A.; Usha Rani, P.; Reddy, P. P., Amino acid disorders in mental retardation: a two-decade study from Andhra Pradesh. Biochem Genet 2004, 42 (3-4), 85-98.
    25. Blau, N.; van Spronsen, F. J.; Levy, H. L., Phenylketonuria. Lancet 2010, 376 (9750), 1417-27.
    26. Russo, P. A.; Mitchell, G. A.; Tanguay, R. M., Tyrosinemia: a review. Pediatr Dev Pathol 2001, 4 (3), 212-21.
    27. Strauss, K. A.; Puffenberger, E. G.; Carson, V. J. J. G., Maple syrup urine disease. 2020.
    28. Dhyani, R.; Shankar, K.; Bhatt, A.; Jain, S.; Hussain, A.; Navani, N. K., Homogentisic Acid-Based Whole-Cell Biosensor for Detection of Alkaptonuria Disease. Anal Chem 2021, 93 (10), 4521-4527.
    29. Williams, R. A.; Mamotte, C. D.; Burnett, J. R., Phenylketonuria: an inborn error of phenylalanine metabolism. Clin Biochem Rev 2008, 29 (1), 31-41.
    30. Hsu, L. W.; Lin, Y. H.; Guo, J. Y.; Chen, C. F.; Chou, Y. J.; Yeh, Y. C., Simultaneous Determination of l-Phenylalanine, Phenylethylamine, and Phenylacetic Acid Using Three-Color Whole-Cell Biosensors within a Microchannel Device. ACS Appl Bio Mater 2020, 3 (8), 5120-5125.
    31. Lin, C.; Jair, Y. C.; Chou, Y. C.; Chen, P. S.; Yeh, Y. C., Transcription factor-based biosensor for detection of phenylalanine and tyrosine in urine for diagnosis of phenylketonuria. Anal Chim Acta 2018, 1041, 108-113.
    32. Longo, N.; Siriwardena, K.; Feigenbaum, A.; Dimmock, D.; Burton, B. K.; Stockler, S.; Waisbren, S.; Lang, W.; Jurecki, E.; Zhang, C.; Prasad, S., Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy. Genet Med 2015, 17 (5), 365-73.
    33. Somaraju, U. R.; Merrin, M., Sapropterin dihydrochloride for phenylketonuria. Cochrane Database Syst Rev 2015, (3), CD008005.
    34. Bell, S. M.; Wendt, D. J.; Zhang, Y.; Taylor, T. W.; Long, S.; Tsuruda, L.; Zhao, B.; Laipis, P.; Fitzpatrick, P. A., Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria. PLoS One 2017, 12 (3), e0173269.
    35. Moat, S. J.; Bradley, D. M.; Salmon, R.; Clarke, A.; Hartley, L., Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK). Eur J Hum Genet 2013, 21 (10), 1049-53.
    36. Cheng, Z.; Ran, Q.; Liu, J.; Deng, X.; Qiu, H.; Jia, Z.; Su, X. J. F. A. M., Rapid Determination for benzoic acid, sorbic acid, phenyllactic acid, phenylalanine, and saccharin sodium in vinegar by high-performance liquid chromatography–UV. 2020, 13 (8), 1673-1680.
    37. Zou, B.; Sun, Y.; Xu, Z.; Chen, Y.; Li, L.; Lin, L.; Zhang, S.; Liao, Q.; Xie, Z., Rapid simultaneous determination of gut microbial phenylalanine, tyrosine, and tryptophan metabolites in rat serum, urine, and faeces using LC-MS/MS and its application to a type 2 diabetes mellitus study. Biomed Chromatogr 2021, 35 (2), e4985.
    38. Kaur, H.; Halliwell, B., Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals. Measurement of hydroxyl radical formation from ozone and in blood from premature babies using improved HPLC methodology. Anal Biochem 1994, 220 (1), 11-5.
    39. Omidinia, E.; Shadjou, N.; Hasanzadeh, M., Aptamer-based biosensor for detection of phenylalanine at physiological pH. Appl Biochem Biotechnol 2014, 172 (4), 2070-80.
    40. Idili, A.; Parolo, C.; Ortega, G.; Plaxco, K. W., Calibration-Free Measurement of Phenylalanine Levels in the Blood Using an Electrochemical Aptamer-Based Sensor Suitable for Point-of-Care Applications. ACS Sens 2019, 4 (12), 3227-3233.
    41. Liu, X.; Zhang, C.; Liu, K.; Wang, H.; Lu, C.; Li, H.; Hua, K.; Zhu, J.; Hui, W.; Cui, Y.; Zhang, X., Multiple SNPs Detection Based on Lateral Flow Assay for Phenylketonuria Diagnostic. Anal Chem 2018, 90 (5), 3430-3436.
    42. Zeng, J.; Spiro, S., Finely tuned regulation of the aromatic amine degradation pathway in Escherichia coli. J Bacteriol 2013, 195 (22), 5141-50.
    43. Diaz, E.; Ferrandez, A.; Prieto, M. A.; Garcia, J. L., Biodegradation of aromatic compounds by Escherichia coli. Microbiol Mol Biol Rev 2001, 65 (4), 523-69, table of contents.
    44. Gabrielli, L.; Rosa-Gastaldo, D.; Salvia, M. V.; Springhetti, S.; Rastrelli, F.; Mancin, F., Detection and identification of designer drugs by nanoparticle-based NMR chemosensing. Chem Sci 2018, 9 (21), 4777-4784.
    45. Breckenridge, A. M.; Breckenridge, R. A.; Peck, C. C., Report on the current status of the use of real-world data (RWD) and real-world evidence (RWE) in drug development and regulation. Br J Clin Pharmacol 2019, 85 (9), 1874-1877.
    46. 濫用藥物尿液檢驗作業準則 https://law.moj.gov.tw/LawClass/LawAll.aspx?pcode=L0030044.
    47. Heal, D. J.; Smith, S. L.; Gosden, J.; Nutt, D. J., Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol 2013, 27 (6), 479-96.
    48. Dragan, A.-M.; Parrilla, M.; Feier, B.; Oprean, R.; Cristea, C.; De Wael, K. J. T. T. i. A. C., Analytical techniques for the detection of amphetamine-type substances in different matrices: A comprehensive review. 2021, 145, 116447.
    49. Teófilo, K. R.; Arantes, L. C.; Marinho, P. A.; Macedo, A. A.; Pimentel, D. M.; Rocha, D. P.; de Oliveira, A. C.; Richter, E. M.; Munoz, R. A.; dos Santos, W. T. J. M. J., Electrochemical detection of 3, 4-methylenedioxymethamphetamine (ecstasy) using a boron-doped diamond electrode with differential pulse voltammetry: Simple and fast screening method for application in forensic analysis. 2020, 157, 105088.
    50. Švorc, Ľ.; Vojs, M.; Michniak, P.; Marton, M.; Rievaj, M.; Bustin, D. J. J. o. E. C., Electrochemical behavior of methamphetamine and its voltammetric determination in biological samples using self-assembled boron-doped diamond electrode. 2014, 717, 34-40.
    51. Rafiee, B.; Fakhari, A. R.; Ghaffarzadeh, M. J. S.; Chemical, A. B., Impedimetric and stripping voltammetric determination of methamphetamine at gold nanoparticles-multiwalled carbon nanotubes modified screen printed electrode. 2015, 218, 271-279.
    52. Merkoci, A.; Alegret, S. J. T. T. i. A. C., New materials for electrochemical sensing IV. Molecular imprinted polymers. 2002, 21 (11), 717-725.
    53. Ivison, F. M.; Kane, J. W.; Pearson, J. E.; Kenny, J.; Vadgama, P. J. E. A. I. J. D. t. F.; Electroanalysis, P. A. o., Development of a redox mediated amperometric detection system for immunoassay. Application to urinary amphetamine screening. 2000, 12 (10), 778-785.
    54. Liu, L.; Wheeler, S. E.; Venkataramanan, R.; Rymer, J. A.; Pizon, A. F.; Lynch, M. J.; Tamama, K., Newly Emerging Drugs of Abuse and Their Detection Methods: An ACLPS Critical Review. Am J Clin Pathol 2018, 149 (2), 105-116.
    55. Chung, H.; Choe, S. J. M. S. L., Amphetamine-type stimulants in drug testing. 2019, 10 (1), 1-10.
    56. Xu, C.; Wang, W.; Wang, S.; Hou, K.; Li, H. J. T. T. i. A. C., Potential analytical methods for on-site oral drug test: Recent developments and applications. 2019, 120, 115649.
    57. Chen, Y. F.; Liu, J. T.; Pan, D. S. J. J. o. t. C. C. S., Discrimination of fluoroamphetamine regioisomers by Raman spectroscopy. 2016, 63 (2), 219-221.
    58. Bell, S. C.; Hanes, R. D., A microfluidic device for presumptive testing of controlled substances. J Forensic Sci 2007, 52 (4), 884-8.
    59. Argente-Garcia, A.; Jornet-Martinez, N.; Herraez-Hernandez, R.; Campins-Falco, P., A solid colorimetric sensor for the analysis of amphetamine-like street samples. Anal Chim Acta 2016, 943, 123-130.
    60. Musile, G.; Wang, L.; Bottoms, J.; Tagliaro, F.; McCord, B. J. A. m., The development of paper microfluidic devices for presumptive drug detection. 2015, 7 (19), 8025-8033.
    61. Negoita, C.; Praisler, M.; Ion, A. In Artificial intelligence application designed to screen for new psychoactive drugs based on their ATR-FTIR spectra, AIP Conference Proceedings, AIP Publishing LLC: 2019; p 170026.
    62. Hargreaves, M. D.; Page, K.; Munshi, T.; Tomsett, R.; Lynch, G.; Edwards, H. G. J. J. o. R. S. A. I. J. f. O. W. i. a. A. o. R. S., Including Higher Order Processes,; Brillouin, a.; Scattering, R., Analysis of seized drugs using portable Raman spectroscopy in an airport environment—a proof of principle study. 2008, 39 (7), 873-880.
    63. Restriction Endonucleases: Molecular Cloning and Beyond. https://international.neb.com/products/restriction-endonucleases/restriction-endonucleases/restriction-endonucleases-molecular-cloning-and-beyond.
    64. Potapov, V.; Ong, J. L.; Kucera, R. B.; Langhorst, B. W.; Bilotti, K.; Pryor, J. M.; Cantor, E. J.; Canton, B.; Knight, T. F.; Evans, T. C., Jr.; Lohman, G. J. S., Comprehensive Profiling of Four Base Overhang Ligation Fidelity by T4 DNA Ligase and Application to DNA Assembly. ACS Synth Biol 2018, 7 (11), 2665-2674.
    65. Push the Limits of Golden Gate Assembly. https://international.neb.com/golden-gate/golden-gate.
    66. KLD Enzyme Mix. https://international.neb.com/products/m0554-kld-enzyme-mix#Product%20Information.
    67. Liu, Y.; Zhuang, Y.; Ding, D.; Xu, Y.; Sun, J.; Zhang, D., Biosensor-Based Evolution and Elucidation of a Biosynthetic Pathway in Escherichia coli. ACS Synth Biol 2017, 6 (5), 837-848.
    68. Lu, S. C.; Liao, W. R.; Chen, S. F., Quantification of Trans-resveratrol in Red Wines Using QuEChERS Extraction Combined with Liquid Chromatography-Tandem Mass Spectrometry. Anal Sci 2018, 34 (4), 439-444.
    69. 食品中游離胺基酸、葡萄糖胺及牛磺酸之檢驗方法. https://consumer.fda.gov.tw/Food/TestingDetail.aspx?nodeID=1037&id=8068.
    70. Kamruzzaman, M.; Alam, A.-M.; Kim, K. M.; Lee, S. H.; Kim, Y. H.; Kim, G.-M.; Dang, T. D. J. F. c., Microfluidic chip based chemiluminescence detection of L-phenylalanine in pharmaceutical and soft drinks. 2012, 135 (1), 57-62.
    71. Cirino, P. C.; Mayer, K. M.; Umeno, D., Generating mutant libraries using error-prone PCR. In Directed evolution library creation, Springer: 2003; pp 3-9.
    72. Yang, J.; Hwang, J. S.; Camakaris, H.; Irawaty, W.; Ishihama, A.; Pittard, J., Mode of action of the TyrR protein: repression and activation of the tyrP promoter of Escherichia coli. Mol Microbiol 2004, 52 (1), 243-56.
    73. Promoters/Catalog/Anderson. http://parts.igem.org/Promoters/Catalog/Anderson.
    74. Reddington, S. C.; Howarth, M. J. C. o. i. c. b., Secrets of a covalent interaction for biomaterials and biotechnology: SpyTag and SpyCatcher. 2015, 29, 94-99.
    75. Lin, Y. K.; Yeh, Y. C., Dual-Signal Microbial Biosensor for the Detection of Dopamine without Inference from Other Catecholamine Neurotransmitters. Anal Chem 2017, 89 (21), 11178-11182.
    76. Liu, Y.; Wan, X.; Wang, B., Engineered CRISPRa enables programmable eukaryote-like gene activation in bacteria. Nat Commun 2019, 10 (1), 3693.
    77. Chen, Y. J.; Liu, P.; Nielsen, A. A.; Brophy, J. A.; Clancy, K.; Peterson, T.; Voigt, C. A., Characterization of 582 natural and synthetic terminators and quantification of their design constraints. Nat Methods 2013, 10 (7), 659-64.
    78. Chen, S. Y.; Wei, W.; Yin, B. C.; Tong, Y.; Lu, J.; Ye, B. C., Development of a Highly Sensitive Whole-Cell Biosensor for Arsenite Detection through Engineered Promoter Modifications. ACS Synth Biol 2019, 8 (10), 2295-2302.

    無法下載圖示 本全文未授權公開
    QR CODE