Application Progress of Genetically Encoded Biosensors in Microbial Cell Factory

doi:10.13523/j.cb.2303019

China Biotechnology

2023, Vol. 43

Issue (9): 62-76 DOI: 10.13523/j.cb.2303019

Application Progress of Genetically Encoded Biosensors in Microbial Cell Factory

HONG Xia^1,²,TIAN Kai-ren³,QIAO Jian-jun^1,^2,³,LI Yan-ni^1,^2,^**(

)

1 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2 Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin 300072, China
3 Zhejiang Institute of Tianjin University (Shaoxing), Shaoxing s312300, China

Download:

HTML

PDF(1713KB) HTML
Export: BibTeX | EndNote (RIS)

Abstract

The rapid development of synthetic biology has promoted the biosynthesis of various complex chemicals in microbial cell factories. However, there are still many problems such as low yield and low production efficiency. Genetically encoded biosensors can sense the fluctuation of intracellular and extracellular metabolite concentration and external environment, and produce measurable signal output or regulate gene expression level in metabolic pathway. Biosensors have aroused widespread attention among synthetic biologists because of their advantages of low cost, simple operation and reproducibility. At present, genetically encoded biosensors have become an important part of synthetic biology and metabolic engineering, and also a powerful tool for metabolic dynamic regulation and ideal phenotype evolution/screening in microbial cell factories. Therefore, the composition and operating principle of genetically encoded biosensors are summarized first, and then, the latest application research of genetically encoded biosensors in dynamic regulation and high-throughput screening of microbial metabolism is emphatically introduced. Finally, the main challenges faced in the design and construction of genetically encoded biosensors are explored, and the future development prospects are discussed.

Key words： Genetically encoded biosensors Synthetic biology Microbial cell factory Dynamic regulation High-throughput screening

Received: 08 March 2023 Published: 08 October 2023

ZTFLH:

Q812

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	Xia HONG
	Kai-ren TIAN
	Jian-jun QIAO
	Yan-ni LI

Cite this article:

HONG Xia, TIAN Kai-ren, QIAO Jian-jun, LI Yan-ni. Application Progress of Genetically Encoded Biosensors in Microbial Cell Factory. China Biotechnology, 2023, 43(9): 62-76.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2303019 OR https://manu60.magtech.com.cn/biotech/Y2023/V43/I9/62

Fig.1 Composition of genetically encoded biosensors

Fig.2 Schematic diagram of biosensors based on transcription factors (a) Biosensors based on activated transcription factors (b) Biosensors based on repressible transcription factors

Fig.3 Schematic diagram of biosensors based on ribosome switch (a) Transcription termination type (b) Translation start-stop type (c) mRNA self-shearing type

Fig.4 Schematic diagram of protein biosensors (a) Two-component system biosensor (b) Fluorescence resonance energy transfer biosensor (c) Application example of enzyme-coupled biosensor

Fig.5 Application of genetically encoded biosensors in the dynamic regulation of microbial metabolism (a) Multifunctional dynamic control system of 4- hydroxyisoleucine^[58] (b) TF biosensor coupled with CRISPRi as NOT gate^[63] (c) Using QS to regulate three different reporter genes independently and sequentially in a single cell^[67] (d) Schematic diagram of joint use of thermal sensor and CRISPRi^[69]

Table 1 Application of genetically encoded biosensors in the dynamic regulation of microbial metabolism

Fig.6 Combining biosensor with high throughput screening method to create HTS platform

Table 2 Application of genetically encoded biosensors in HTS


[1]	Gupta N, Renugopalakrishnan V, Liepmann D, et al. Cell-based biosensors: recent trends, challenges and future perspectives. Biosensors & Bioelectronics, 2019, 141: 111435. doi: 10.1016/j.bios.2019.111435

[2]	Liu C J, Yu H, Zhang B C, et al. Engineering whole-cell microbial biosensors: design principles and applications in monitoring and treatment of heavy metals and organic pollutants. Biotechnology Advances, 2022, 60: 108019. doi: 10.1016/j.biotechadv.2022.108019

[3]	Zhu Y, Elcin E, Jiang M Y, et al. Use of whole-cell bioreporters to assess bioavailability of contaminants in aquatic systems. Frontiers in Chemistry, 2022, 10: 1018124. doi: 10.3389/fchem.2022.1018124

[4]	Jeon Y, Lee Y J, Kim K, et al. Transcription factor-based biosensors for detecting pathogens. Biosensors, 2022, 12(7): 470. doi: 10.3390/bios12070470

[5]	Zhang Y M, Shi S B. Transcription factor-based biosensor for dynamic control in yeast for natural product synthesis. Frontiers in Bioengineering and Biotechnology, 2021, 9: 635265. doi: 10.3389/fbioe.2021.635265

[6]	Teng Y X, Zhang J L, Jiang T, et al. Biosensor-enabled pathway optimization in metabolic engineering. Current Opinion in Biotechnology, 2022, 75: 102696. doi: 10.1016/j.copbio.2022.102696

[7]	Sun X, Li Q G, Wang Y, et al. Isoleucyl-tRNA synthetase mutant based whole-cell biosensor for high-throughput selection of isoleucine overproducers. Biosensors and Bioelectronics, 2021, 172: 112783. doi: 10.1016/j.bios.2020.112783

[8]	Tellechea-Luzardo J, Stiebritz M T, Carbonell P. Transcription factor-based biosensors for screening and dynamic regulation. Frontiers in Bioengineering and Biotechnology, 2023, 11: 1118702. doi: 10.3389/fbioe.2023.1118702

[9]	Xiao D, Hu C X, Xu X Z, et al. A d, l-lactate biosensor based on allosteric transcription factor LldR and amplified luminescent proximity homogeneous assay. Biosensors & Bioelectronics, 2022, 211: 114378. doi: 10.1016/j.bios.2022.114378

[10]	Paulius M, Ingrida K, Ernesta A, et al. Development and characterization of indole-responsive whole-cell biosensor based on the inducible gene expression system from Pseudomonas putida KT2440. International Journal of Molecular Sciences, 2022, 23(9): 4649. doi: 10.3390/ijms23094649

[11]	Pereira H, Azevedo F, Domingues L, et al. Expression of Yarrowia lipolytica acetyl-CoA carboxylase in Saccharomyces cerevisiae and its effect on in-vivo accumulation of Malonyl-CoA. Computational and Structural Biotechnology Journal, 2022, 20: 779-787. doi: 10.1016/j.csbj.2022.01.020

[12]	Jiang T, Li C Y, Zou Y S, et al. Establishing an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system for improved pathway performance. Metabolic Engineering, 2022, 74: 1-10. doi: 10.1016/j.ymben.2022.08.009

[13]	Piorino F, Styczynski M P. Harnessing Escherichia coli’s native machinery for detection of vitamin C (ascorbate) deficiency. ACS Synthetic Biology, 2022. DOI:10.1021/acssynbio.2c00335. doi: 10.1021/acssynbio.2c00335

[14]	Wang S M, Jiang W, Jin X, et al. Genetically encoded ATP and NAD(P)H biosensors: potential tools in metabolic engineering. Critical Reviews in Biotechnology, 2022, 21: 1-15. doi: 10.1080/20013891081665

[15]	Wan X, Marsafari M, Xu P. Engineering metabolite-responsive transcriptional factors to sense small molecules in eukaryotes: current state and perspectives. Microbial Cell Factories, 2019, 18(1): 1-13. doi: 10.1186/s12934-018-1049-x

[16]	Ellis J, Wolfgang M. A genetically encoded metabolite sensor for malonyl-CoA. Chemistry & Biology, 2012, 19(10): 1333-1339. doi: 10.1016/j.chembiol.2012.08.018

[17]	Stanton B C, Siciliano V, Ghodasara A, et al. Systematic transfer of prokaryotic sensors and circuits to mammalian cells. ACS Synthetic Biology, 2014, 3(12): 880-891. doi: 10.1021/sb5002856 pmid: 25360681

[18]	Byun J. Recent progress and opportunities for nucleic acid aptamers. Life, 2021, 11(3): 193. doi: 10.3390/life11030193

[19]	Wrist A, Sun W Q, Summers R M. The theophylline aptamer: 25 years as an important tool in cellular engineering research. ACS Synthetic Biology, 2020, 9(4): 682-697. doi: 10.1021/acssynbio.9b00475 pmid: 32142605

[20]	Huang P J J, Liu J W. A DNA aptamer for theophylline with ultrahigh selectivity reminiscent of the classic RNA aptamer. ACS Chemical Biology, 2022, 17(8): 2121-2129. doi: 10.1021/acschembio.2c00179

[21]	Deng J Y, Chen C M, Gu Y, et al. Creating an in vivo bifunctional gene expression circuit through an aptamer-based regulatory mechanism for dynamic metabolic engineering in Bacillus subtilis. Metabolic Engineering, 2019, 55: 179-190. doi: 10.1016/j.ymben.2019.07.008

[22]	Li C Y, Jiang T, Li M, et al. Fine-tuning gene expression for improved biosynthesis of natural products: from transcriptional to post-translational regulation. Biotechnology Advances, 2022, 54: 107853. doi: 10.1016/j.biotechadv.2021.107853

[23]	Hossain G S, Saini M, Miyake R, et al. Genetic biosensor design for natural product biosynthesis in microorganisms. Trends in Biotechnology, 2020, 38(7): 797-810. doi: S0167-7799(20)30088-3 pmid: 32359951

[24]	Wu Y F, Zhu L J, Li S T, et al. High content design of riboswitch biosensors: all-around rational module-by-module design. Biosensors and Bioelectronics, 2023, 220: 114887. doi: 10.1016/j.bios.2022.114887

[25]	Zhou L B, Ren J, Li Z D, et al. Characterization and engineering of a Clostridium glycine riboswitch and its use to control a novel metabolic pathway for 5-aminolevulinic acid production in Escherichia coli. ACS Synthetic Biology, 2019, 8(10): 2327-2335. doi: 10.1021/acssynbio.9b00137

[26]	Antunes D, Jorge N A N, Garcia de Souza Costa M, et al. Unraveling RNA dynamical behavior of TPP riboswitches: a comparison between Escherichia coli and Arabidopsis thaliana. Scientific Reports, 2019, 9(1): 1-13. doi: 10.1038/s41598-018-37186-2

[27]	Martin J E, Le M T, Bhattarai N, et al. A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus. Nucleic Acids Research, 2019, 47(13): 6885-6899. doi: 10.1093/nar/gkz494 pmid: 31165873

[28]	Lazar J T, Tabor J J. Bacterial two-component systems as sensors for synthetic biology applications. Current Opinion in Systems Biology, 2021, 28: 100398. doi: 10.1016/j.coisb.2021.100398

[29]	Schmidl S R, Ekness F, Sofjan K, et al. Rewiring bacterial two-component systems by modular DNA-binding domain swapping. Nature Chemical Biology, 2019, 15(7): 690-698. doi: 10.1038/s41589-019-0286-6 pmid: 31110305

[30]	Del Valle I, Fulk E M, Kalvapalle P, et al. Translating new synthetic biology advances for biosensing into the earth and environmental sciences. Frontiers in Microbiology, 2021, 11: 618373. doi: 10.3389/fmicb.2020.618373

[31]	Wu Y X, Jiang T Y. Developments in FRET- and BRET-based biosensors. Micromachines, 2022, 13(10): 1789. doi: 10.3390/mi13101789

[32]	Zhang X J, Hu Y, Yang X T, et al. Förster resonance energy transfer (FRET)-based biosensors for biological applications. Biosensors and Bioelectronics, 2019, 138: 111314. doi: 10.1016/j.bios.2019.05.019

[33]	Pfleger K D G, Seeber R M, Eidne K A. Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nature Protocols, 2006, 1(1): 337-345. pmid: 17406254

[34]	Kaku T, Sugiura K, Entani T, et al. Enhanced brightness of bacterial luciferase by bioluminescence resonance energy transfer. Scientific Reports, 2021, 11(1): 1-10. doi: 10.1038/s41598-020-79139-8

[35]	Yang J, Cumberbatch D, Centanni S, et al. Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing. Nature Communications, 2016, 7(1): 1-10.

[36]	Singh S, Sharma M P, Alqarawi A A, et al. Real-time optical detection of isoleucine in living cells through a genetically-encoded nanosensor. Sensors (Basel, Switzerland), 2019, 20(1): 146. doi: 10.3390/s20010146

[37]	Soleja N, Agrawal N, Nazir R, et al. Enhanced sensitivity and detection range of FRET-based vitamin B12 nanosensor. 3 Biotech, 2020, 10(3): 1-13. doi: 10.1007/s13205-019-1978-z

[38]	Hall M D, Simeonov A, Davis M I. Avoiding fluorescence assay interference: the case for diaphorase. ASSAY and Drug Development Technologies, 2016, 14(3): 175-179. doi: 10.1089/adt.2016.707

[39]	Lin J L, Ekas H, Markham K, et al. An enzyme-coupled assay enables rapid protein engineering for geraniol production in yeast. Biochemical Engineering Journal, 2018, 139: 95-100. doi: 10.1016/j.bej.2018.08.011

[40]	Yang D, Kim W J, Yoo S M, et al. Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(40): 9835-9844.

[41]	Kroll J B, Schwarzländer M, Smith E N. NAD redox monitoring with the genetically encoded fluorescent biosensor Peredox-mCherry. Trends in Plant Science, 2021, 26(10): 1087-1088. doi: 10.1016/j.tplants.2021.06.017 pmid: 34340932

[42]	Hirano M, Ando R, Shimozono S, et al. A highly photostable and bright green fluorescent protein. Nature Biotechnology, 2022, 40(7): 1132-1142. doi: 10.1038/s41587-022-01278-2

[43]	Shaner N C, Campbell R E, Steinbach P A, et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nature Biotechnology, 2004, 22(12): 1567-1572. doi: 10.1038/nbt1037

[44]	Anderson M R, Padgett C M, Dargatz C J, et al. Engineering a yellow thermostable fluorescent protein by rational design. ACS Omega, 2023, 8(1): 436-443. doi: 10.1021/acsomega.2c05005 pmid: 36643458

[45]	Lambert T J. FPbase: a community-editable fluorescent protein database. Nature Methods, 2019, 16(4): 277-278.

[46]	Lopreside A, Wan X Y, Michelini E, et al. Comprehensive profiling of diverse genetic reporters with application to whole-cell and cell-free biosensors. Analytical Chemistry, 2019, 91(23): 15284-15292. doi: 10.1021/acs.analchem.9b04444 pmid: 31690077

[47]	Watstein D M, Styczynski M P. Development of a pigment-based whole-cell zinc biosensor for human serum. ACS Synthetic Biology, 2018, 7(1): 267-275. doi: 10.1021/acssynbio.7b00292 pmid: 29202581

[48]	Davis R W IV, Muse C G, Eggleston H, et al. Sugar shock: probing Streptococcus pyogenes metabolism through bioluminescence imaging. Frontiers in Microbiology, 2022, 13: 864014. doi: 10.3389/fmicb.2022.864014

[49]	Feeney K A, Putker M, Brancaccio M, et al. In-depth characterization of firefly luciferase as a reporter of circadian gene expression in mammalian cells. Journal of Biological Rhythms, 2016, 31(6): 540-550. doi: 10.1177/0748730416668898 pmid: 28112045

[50]	Sato W, Rasmussen M, Deich C, et al. Expanding luciferase reporter systems for cell-free protein expression. Scientific Reports, 2022, 12(1): 11489. doi: 10.1038/s41598-022-15624-6 pmid: 35798760

[51]	Hall M P, Unch J, Binkowski B F, et al. Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chemical Biology, 2012, 7(11): 1848-1857. doi: 10.1021/cb3002478 pmid: 22894855

[52]	Calabretta M M, Gregucci D, Martínez-Pérez-Cejuela H, et al. A luciferase mutant with improved brightness and stability for whole-cell bioluminescent biosensors and in vitro biosensing. Biosensors, 2022, 12(9): 742. doi: 10.3390/bios12090742

[53]	Mitchler M M, Garcia J M, Montero N E, et al. Transcription factor-based biosensors: a molecular-guided approach for natural product engineering. Current Opinion in Biotechnology, 2021, 69: 172-181. doi: 10.1016/j.copbio.2021.01.008 pmid: 33493842

[54]	Boada Y, Vignoni A, Picó J, et al. Extended metabolic biosensor design for dynamic pathway regulation of cell factories. iScience, 2020, 23(7): 101305. doi: 10.1016/j.isci.2020.101305

[55]	Yu W W, Xu X H, Jin K, et al. Genetically encoded biosensors for microbial synthetic biology: from conceptual frameworks to practical applications. Biotechnology Advances, 2023, 62: 108077. doi: 10.1016/j.biotechadv.2022.108077

[56]	Li Z D, Gao C, Ye C, et al. Systems engineering of Escherichia coli for high-level shikimate production. Metabolic Engineering, 2023, 75: 1-11. doi: 10.1016/j.ymben.2022.10.010

[57]	Zhu Y, Li Y, Xu Y, et al. Development of bifunctional biosensors for sensing and dynamic control of glycolysis flux in metabolic engineering. Metabolic Engineering, 2021, 68: 142-151. doi: 10.1016/j.ymben.2021.09.011 pmid: 34610458

[58]	Lai W M, Shi F, Tan S Y, et al. Dynamic control of 4-hydroxyisoleucine biosynthesis by multi-biosensor in Corynebacterium glutamicum. Applied Microbiology and Biotechnology, 2022, 106(13-16): 5105-5121. doi: 10.1007/s00253-022-12034-6

[59]	Ali S A, Mittal D, Kaur G. In-situ monitoring of xenobiotics using genetically engineered whole-cell-based microbial biosensors: recent advances and outlook. World Journal of Microbiology and Biotechnology, 2021, 37(5): 1-24. doi: 10.1007/s11274-020-02944-w

[60]	Wang W J, Zhang J, Tao H, et al. E. coli biosensor based on modular GFP and LuxI/luxR cyclic amplification circuit for sensitive detection of lysine. Analytical and Bioanalytical Chemistry, 2022, 414(29-30): 8299-8307. doi: 10.1007/s00216-022-04364-1

[61]	He X Y, Chen Y, Liang Q F, et al. Autoinduced AND gate controls metabolic pathway dynamically in response to microbial communities and cell physiological state. ACS Synthetic Biology, 2017, 6(3): 463-470. doi: 10.1021/acssynbio.6b00177 pmid: 27997131

[62]	Nozzi N E, Case A E, Carroll A L, et al. Systematic approaches to efficiently produce 2, 3-butanediol in a marine Cyanobacterium. ACS Synthetic Biology, 2017, 6(11): 2136-2144. doi: 10.1021/acssynbio.7b00157

[63]	Zhao M, Li Y T, Wang F Q, et al. A CRISPRi mediated self-inducible system for dynamic regulation of TCA cycle and improvement of itaconic acid production in Escherichia coli. Synthetic and Systems Biotechnology, 2022, 7(3): 982-988. doi: 10.1016/j.synbio.2022.05.008

[64]	Choi J, Ahn J, Bae J, et al. Recent synthetic biology approaches for temperature- and light-controlled gene expression in bacterial hosts. Molecules, 2022, 27(20): 6798. doi: 10.3390/molecules27206798

[65]	Gu P F, Ma Q Q, Zhao S, et al. Application of quorum sensing system in microbial synthesis of valuable chemicals: a mini-review. World Journal of Microbiology and Biotechnology, 2022, 38(11): 192. doi: 10.1007/s11274-022-03382-6

[66]	Wu S B, Xue Y T, Yang S J, et al. Combinational quorum sensing devices for dynamic control in cross-feeding cocultivation. Metabolic Engineering, 2021, 67: 186-197. doi: 10.1016/j.ymben.2021.07.002 pmid: 34229080

[67]	Ge C, Yu Z, Sheng H K, et al. Redesigning regulatory components of quorum-sensing system for diverse metabolic control. Nature Communications, 2022, 13(1): 1-12. doi: 10.1038/s41467-021-27699-2

[68]	Chee W K D, Yeoh J W, Dao V L, et al. Thermogenetics: Applications come of age. Biotechnology Advances, 2022, 55: 107907. doi: 10.1016/j.biotechadv.2022.107907

[69]	Yu W W, Jin K, Wu Y K, et al. A pathway independent multi-modular ordered control system based on thermosensors and CRISPRi improves bioproduction in Bacillus subtilis. Nucleic Acids Research, 2022, 50(11): 6587-6600. doi: 10.1093/nar/gkac476

[70]	Wang X, Han J N, Zhang X, et al. Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli. Nature Communications, 2021, 12(1): 1-13. doi: 10.1038/s41467-020-20314-w

[71]	Shen B, Zhou P P, Jiao X, et al. Fermentative production of vitamin E tocotrienols in Saccharomyces cerevisiae under cold-shock-triggered temperature control. Nature Communications, 2020, 11(1): 1-14. doi: 10.1038/s41467-019-13993-7

[72]	Bañares A B, Valdehuesa K N G, Ramos K R M, et al. A pH-responsive genetic sensor for the dynamic regulation of D-xylonic acid accumulation in Escherichia coli. Applied Microbiology and Biotechnology, 2020, 104(5): 2097-2108. doi: 10.1007/s00253-019-10297-0 pmid: 31900554

[73]	Ohlendorf R, Möglich A. Light-regulated gene expression in Bacteria: Fundamentals, advances, and perspectives. Frontiers in Bioengineering and Biotechnology, 2022, 10: 1029403. doi: 10.3389/fbioe.2022.1029403

[74]	Multamäki E, García de Fuentes A, Sieryi O, et al. Optogenetic control of bacterial expression by red light. ACS Synthetic Biology, 2022, 11(10): 3354-3367. doi: 10.1021/acssynbio.2c00259 pmid: 35998606

[75]	Castillo-Hair S M, Baerman E A, Fujita M, et al. Optogenetic control of Bacillus subtilis gene expression. Nature Communications, 2019, 10(1): 1-11. doi: 10.1038/s41467-018-07882-8

[76]	Li X M, Jiang W, Qi Q S, et al. A gene circuit combining the endogenous I-E type CRISPR-cas system and a light sensor to produce poly-β-hydroxybutyric acid efficiently. Biosensors, 2022, 12(8): 642. doi: 10.3390/bios12080642

[77]	Zhu Y, Gao H X, Zhang J, et al. De novo design of the global transcriptional factor Cra-regulated promoters enables highly sensitive glycolysis flux biosensor for dynamic metabolic control. Microbial Biotechnology, 2023, 16(3): 605-617. doi: 10.1111/mbt2.v16.3

[78]	Miyake R, Ling H, Foo J L, et al. Transporter-driven engineering of a genetic biosensor for the detection and production of short-branched chain fatty acids in Saccharomyces cerevisiae. Frontiers in Bioengineering and Biotechnology, 2022, 10: 838732. doi: 10.3389/fbioe.2022.838732

[79]	Boada Y, Santos-Navarro F N, Picó J, et al. Modeling and optimization of a molecular biocontroller for the regulation of complex metabolic pathways. Frontiers in Molecular Biosciences, 2022, 9: 801032. doi: 10.3389/fmolb.2022.801032

[80]	Liu D, Sica M S, Mao J W, et al. A p-coumaroyl-CoA biosensor for dynamic regulation of naringenin biosynthesis in Saccharomyces cerevisiae. ACS Synthetic Biology, 2022, 11(10): 3228-3238. doi: 10.1021/acssynbio.2c00111

[81]	Lalwani M A, Ip S S, Carrasco-López C, et al. Optogenetic control of the lac operon for bacterial chemical and protein production. Nature Chemical Biology, 2021, 17(1): 71-79. doi: 10.1038/s41589-020-0639-1

[82]	Hong K Q, Zhang J, Jin B, et al. Development and characterization of a glycine biosensor system for fine-tuned metabolic regulation in Escherichia coli. Microbial Cell Factories, 2022, 21: 56. doi: 10.1186/s12934-022-01779-4

[83]	Yang X Y, Liu J H, Zhang J, et al. Quorum sensing-mediated protein degradation for dynamic metabolic pathway control in Saccharomyces cerevisiae. Metabolic Engineering, 2021, 64: 85-94. doi: 10.1016/j.ymben.2021.01.010

[84]	Fernández-Cabezón L, Rosich i Bosch B, Kozaeva E, et al. Dynamic flux regulation for high-titer anthranilate production by plasmid-free, conditionally-auxotrophic strains of Pseudomonas putida. Metabolic Engineering, 2022, 73: 11-25. doi: 10.1016/j.ymben.2022.05.008 pmid: 35659519

[85]	Li C F, Wang C, Zhu J, et al. Advances and prospects of transcription-factor-based biosensors in high-throughput screening for cell factories construction. Food Bioengineering, 2022, 1(2): 135-147. doi: 10.1002/fbe2.v1.2

[86]	Qiu X L, Xu P, Zhao X R, et al. Combining genetically-encoded biosensors with high throughput strain screening to maximize erythritol production in Yarrowia lipolytica. Metabolic Engineering, 2020, 60: 66-76. doi: 10.1016/j.ymben.2020.03.006

[87]	Qian S, Li Y, Cirino P C. Biosensor-guided improvements in salicylate production by recombinant Escherichia coli. Microbial Cell Factories, 2019, 18(1): 1-9. doi: 10.1186/s12934-018-1049-x

[88]	Chen D D, Xu S M, Li S L, et al. Directly evolved AlkS-based biosensor platform for monitoring and high-throughput screening of alkane production. ACS Synthetic Biology, 2023, 12(3): 832-841. doi: 10.1021/acssynbio.2c00620 pmid: 36779413

[89]	Gao J S, Du M H, Zhao J H, et al. Design of a genetically encoded biosensor to establish a high-throughput screening platform for L-cysteine overproduction. Metabolic Engineering, 2022, 73: 144-157. doi: 10.1016/j.ymben.2022.07.007 pmid: 35921946

[90]	Hengoju S, Tovar M, Man D K W, et al. Droplet microfluidics for microbial biotechnology. Microfluidics in Biotechnology. Cham: Springer International Publishing, 2020: 129-157.

[91]	Sun G Y, Wu Y K, Huang Z Y, et al. Directed evolution of diacetylchitobiose deacetylase via high-throughput droplet sorting with a novel, bacteria-based biosensor. Biosensors and Bioelectronics, 2023, 219: 114818. doi: 10.1016/j.bios.2022.114818

[92]	Tu R, Li L P, Yuan H L, et al. Biosensor-enabled droplet microfluidic system for the rapid screening of 3-dehydroshikimic acid produced in Escherichia coli. Journal of Industrial Microbiology and Biotechnology, 2020, 47(12): 1155-1160. doi: 10.1007/s10295-020-02316-1

[93]	Ma F Q, Chung M T, Yao Y, et al. Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform. Nature Communications, 2018, 9(1): 1-8. doi: 10.1038/s41467-017-02088-w

[94]	Henkel T, Mayer G, Hampl J, et al. From microtiter plates to droplets: there and back again. Micromachines, 2022, 13(7): 1022. doi: 10.3390/mi13071022

[95]	Zhang J, Li Q B, Wang Q, et al. Heme biosensor-guided in vivo pathway optimization and directed evolution for efficient biosynthesis of heme. Biotechnology for Biofuels and Bioproducts, 2023, 16(1): 33. doi: 10.1186/s13068-023-02285-4

[96]	Wang J, Li C Y, Jiang T, et al. Biosensor-assisted titratable CRISPRi high-throughput (BATCH) screening for over-production phenotypes. Metabolic Engineering, 2023, 75: 58-67. doi: 10.1016/j.ymben.2022.11.004

[97]	Li C, Gao X, Qi H B, et al. Substantial improvement of an epimerase for the synthesis of D-allulose by biosensor-based high-throughput microdroplet screening. Angewandte Chemie International Edition, 2023, 62(10): e202216721.

[98]	Han G Q, Xu N, Sun X P, et al. Improvement of l-valine production by atmospheric and room temperature plasma mutagenesis and high-throughput screening in Corynebacterium glutamicum. ACS Omega, 2020, 5(10): 4751-4758. doi: 10.1021/acsomega.9b02747

[99]	Hua E B, Zhang Y, Yun K Y, et al. Whole-cell biosensor and producer Co-cultivation-based microfludic platform for screening Saccharopolyspora erythraea with hyper erythromycin production. ACS Synthetic Biology, 2022, 11(8): 2697-2708. doi: 10.1021/acssynbio.2c00102

[100]	D’Oelsnitz S, Kim W, Burkholder N T, et al. Using fungible biosensors to evolve improved alkaloid biosyntheses. Nature Chemical Biology, 2022, 18(9): 981-989. doi: 10.1038/s41589-022-01072-w pmid: 35799063

[101]	Han L C, Liu X Y, Cheng Z Y, et al. 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 Synthetic Biology, 2022, 11(4): 1577-1587. doi: 10.1021/acssynbio.1c00642

[102]	Yuan S F, Nair P H, Borbon D, et al. Metabolic engineering of E. coli for β-alanine production using a multi-biosensor enabled approach. Metabolic Engineering, 2022, 74: 24-35. doi: 10.1016/j.ymben.2022.08.012

[103]	Du Y X, Zhang X Y, Zhang H W, et al. Direct evolution of riboflavin kinase significantly enhance flavin mononucleotide synthesis by design and optimization of flavin mononucleotide riboswitch. Bioresource Technology, 2023, 381: 128774. doi: 10.1016/j.biortech.2023.128774

[104]	Liu Y F, Yuan H L, Ding D Q, et al. Establishment of a biosensor-based high-throughput screening platform for tryptophan overproduction. ACS Synthetic Biology, 2021, 10(6): 1373-1383. doi: 10.1021/acssynbio.0c00647 pmid: 34081459

[105]	Deng C, Wu Y K, Lv X Q, et al. Refactoring transcription factors for metabolic engineering. Biotechnology Advances, 2022, 57: 107935. doi: 10.1016/j.biotechadv.2022.107935

[106]	Tapsin S, Sun M, Shen Y, et al. Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes. Nature Communications, 2018, 9(1): 1-10. doi: 10.1038/s41467-017-02088-w

[107]	El-Husseini D M, Sayour A E, Melzer F, et al. Generation and selection of specific aptamers targeting Brucella species through an enhanced cell-SELEX methodology. International Journal of Molecular Sciences, 2022, 23(11): 6131. doi: 10.3390/ijms23116131

[108]	Jagodnik J, Tjaden B, Ross W, et al. Identification and characterization of RNA binding sites for (p)ppGpp using RNA-DRaCALA. Nucleic Acids Research, 2023, 51(2): 852-869. doi: 10.1093/nar/gkac1224 pmid: 36617997

[109]	Zhang J, Pang Q X, Wang Q, et al. Modular tuning engineering and versatile applications of genetically encoded biosensors. Critical Reviews in Biotechnology, 2022, 42(7): 1010-1027. doi: 10.1080/07388551.2021.1982858

[110]	Khoshbin Z, Housaindokht M R, Izadyar M, et al. Recent advances in computational methods for biosensor design. Biotechnology and Bioengineering, 2021, 118(2): 555-578. doi: 10.1002/bit.27618 pmid: 33135778

[111]	Ma Z L, Meliana C, Munawaroh H S H, et al. Recent advances in the analytical strategies of microbial biosensor for detection of pollutants. Chemosphere, 2022, 306: 135515. doi: 10.1016/j.chemosphere.2022.135515

[112]	Ding N N, Zhou S H, Deng Y. Transcription-factor-based biosensor engineering for applications in synthetic biology. ACS Synthetic Biology, 2021, 10(5): 911-922. doi: 10.1021/acssynbio.0c00252

[113]	Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873): 583-589. doi: 10.1038/s41586-021-03819-2

[1]	ZUO Kun-lan, ZOU Shi-shi, WU Zong-zhen, GUO Yuan-yuan, XU Yan-long, LIU Huan. Biosafety Risks and Countermeasures of Pathogen Related Synthetic Biology[J]. China Biotechnology, 2023, 43(9): 120-130.

[2]	Jia-wen LI, Yu-xuan FAN, Fu-li LI, Zhao-hui ZHANG, Shi-an WANG. Ide.pngication of Short Peptides from Oleosin for Lipid Droplet Localization in Xanthophyllomyces dendrorhous[J]. China Biotechnology, 2023, 43(7): 36-43.

[3]	FU Meng-meng, SU Dan-dan, ZUO Kun-lan, WU Zong-zhen, LI Si-si, XU Yan-long, LIU Huan. Biosafety Risks of Synthetic Biology Related to Human Immunity and The Countermeaseures[J]. China Biotechnology, 2023, 43(6): 125-132.

[4]	LI Yu-tong, CUI Tian-qi, ZHANG Hai-lin, YU Guang-le, LUAN Ji, WANG Hai-long. *Research Advances in Tumor-targeting Bacteria Escherichia coli* Nissle 1917 in Cancer Therapy**[J]. China Biotechnology, 2023, 43(6): 54-68.

[5]	LIU Ting-ting, ZHANG Ping, ZHANG Yue. Regulation Role of Light-controlled Expression Systems in Synthetic Biology[J]. China Biotechnology, 2023, 43(4): 92-100.

[6]	NING Jun-tao, ZOU Shi-shi, ZUO Kun-lan, WU Zong-zhen, Li Jing, XU Yan-long, LIU Huan. Biosafety Risks and Countermeasures of Active Substance in Synthesis Biology[J]. China Biotechnology, 2023, 43(2/3): 180-189.

[7]	YANG Yang, YAO Ming-dong, WANG Ying, XIAO Wen-hai. Research Progress of Synthesis of 2'-Fucosyllactose by Yeast[J]. China Biotechnology, 2023, 43(1): 127-138.

[8]	Nan JIA,Guo-wei ZANG,Chun LI,Ying WANG. Metabolic Regulations and Applications of Cofactors in Microbial Cell Factories[J]. China Biotechnology, 2022, 42(7): 79-89.

[9]	Xue-xia ZENG,Yu DAN,Shao-ming MAO,Jia-hui SUN,Guo-dong LUAN,Xue-feng LV. Research Progress on the Cyanobacterial Photosynthetic Production of Sugars Utilizing Carbon Dioxide[J]. China Biotechnology, 2022, 42(7): 90-100.

[10]	ZHANG Da-lu,GE Qi,FENG Yi-bo,CHEN Wei-gang. Comparison and Analysis on Scientific Research Programs on DNA Data Storage[J]. China Biotechnology, 2022, 42(6): 116-129.

[11]	BAI Song,HOU Zheng-jie,GAO Geng-rong,QIAO Bin,CHENG Jing-sheng. Advances in the Synthesis of Odd-chain Fatty Acids by Microorganisms[J]. China Biotechnology, 2022, 42(6): 76-85.

[12]	LIANG Shi-yu,WAN Li,GUO Xiao-jia,WANG Xue-ying,LV Li-ting,HU Ying-han,ZHAO Zong-bao. *Engineered Rhodosporidium toruloides* Strains Capable of Biosynthesizing a Non-natural Cofactor**[J]. China Biotechnology, 2022, 42(5): 58-68.

[13]	ZHAO Chi-hong,SU Dan-dan,LI Chun,WU Zong-zhen,ZUO Kun-lan,XU Yan-long,LIU Huan. Synthetic Biology Risks and Biosafety Strategies in the View of Overall National Security Concept[J]. China Biotechnology, 2022, 42(12): 120-128.

[14]	Chun-li HAN,Han-jie WANG. Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy[J]. China Biotechnology, 2022, 42(10): 39-50.

[15]	Hui-min LI,Bin JIA,Xia LI,Duo LIU. Advances in Engineering Yeast Chassis for Producing Aromatic Compounds[J]. China Biotechnology, 2022, 42(10): 80-92.

Viewed

Full text

Abstract

Cited

Shared

Discussed