Application of Transcription Factor-based Biosensors in Environmental Analysis

doi:10.13560/j.cnki.biotech.bull.1985.2023-1184

Abstract

Abstract:

Transcription factors are a class of proteins that regulate gene expression in cells by directing RNA polymerases to bind to specific DNA sequences. Transcription factors, as important regulatory proteins for prokaryotes to adapt to the natural environment, can specifically sense ligand molecules in environmental media. By coupling with different signal transduction and amplification systems, biosensing systems with transcription factors as recognition elements can construct flexible sensing strategies in whole-cell system, cell-free system and in vitro reaction systems. The transcription factor-based biosensors（TFBBs）have the advantages of high sensitivity, small size, low-cost, and on-site monitoring, showing great potential in the analysis of environmental pollutants. This paper introduces the reaction system types, core component compositions and working principle of TFBBs, as well as lists their application progress in the detection of environmental pollutants including heavy metal ions, aromatic compounds and antibiotics. On this basis, the opportunities and challenges for TFBBs in the detection of environmental pollutants are discussed, and the development trend of TFBBs is prospected. It points out that the rapid development of interdisciplinary emerging technologies such as synthetic biology and artificial intelligence will promote the artificial design and sensing performance improvement of TFBBs, making them applicable in a wider range of fields.

Key words: transcription factors, biosensor, environmental analysis, heavy metal ions, aromatic compounds, antibiotics

ZHANG Di, JU Rui, LI Li-mei, WANG Yu-qian, CHEN Rui, WANG Xin-yi. Application of Transcription Factor-based Biosensors in Environmental Analysis[J]. Biotechnology Bulletin, 2024, 40(6): 114-125.

Figures/Tables 4

References 97

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重金属 Heavy metal ion	转录因子/家族 TFs/families	PDB	反应平台 Reaction platform	报告元件 Report component	检测限 Limit of detection	参考文献 Reference
汞Hg（II）	MerR/MerR	-	全细胞平台	mCherry	0.1 nmol/L	[33]
			全细胞平台	GFP	4.4 nmol/L	[24]
			全细胞平台	RFP	1 mg/kg	[32]
			无细胞平台	3WJdB	0.5 nmol/L	[40]
			全细胞平台	sfCherry3C	2.24 µmol/L	[41]
	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
镉Cd（II）	ZntR/MerR	1Q08	全细胞平台	sGFP	35 nmol/L	[42]
			全细胞平台	eGFP	1 000 nmol/L	[43]
			全细胞平台	Lux	100 nmol/L	[44]
	MerR/MerR	-	全细胞平台	GFP	283.9 nmol/L	[24]
	MerR/MerR	-	全细胞平台	eGFP	3 µmol/L	[45]
	CadC/ArsR/SmtB	1U2W	全细胞平台	GFP	10 µg/mL	[46]
	CadR/MerR	-	全细胞平台	mCherry	0.1 µg/mL	[47]
	ZntR/MerR	1Q08	全细胞平台	GFP	5 µmol/L	[35]
砷As（III）	ArsR/ArsR/SmtB	1R23	邻近效应驱动	Lac Z	8 ppb	[48]
	ArsR/ArsR/SmtB	-	全细胞平台	GFP	0.1 µmol/L	[36]
	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
铜Cu（II）	CopR/CopY	-	全细胞平台	RFP	24.3 µmol/L	[49]
	CueR/MerR	1Q05	全细胞平台	eGFP	0.08 µmol/L	[50]
	CusR	-	全细胞平台	GFP	12 µmol/L	[36]
锌Zn（II）	SmtB/ArsR/SmtB	1R23	全细胞平台	eGFP	1 µmol/L	[51]
	ZntR/MerR	1Q08	全细胞平台	GFP、mCherry	5 mg/L	[52]
	MerRZntR/MerR	-	全细胞平台	eGFP、mCherry	10 µg/mL	[53]
	MerRZntR/MerR	-	全细胞平台	Lux	0.03 mmol/L	[54]
铅Pb（II）	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
	MerR/MerR	-	全细胞平台	GFP	39.6 nmol/L	[24]
	PbrR/MerR	-	全细胞平台	靛蓝合成酶Indigoidine synthetase	0.065 mol/L	[55]
			无细胞平台	3WJdB	0.1 nmol/L	[40]
			全细胞平台	比色法	2.93 nmol/L	[56]
锑Sb（III）	ArsR/ArsR/SmtB	1R23	全细胞平台	eGFP	0.25 µmol/L	[57]
镍Ni（II）	RcnR/CsoR-RcnR	-	全细胞平台	Lux	80 nmol/L	[37]

重金属 Heavy metal ion	转录因子/家族 TFs/families	PDB	反应平台 Reaction platform	报告元件 Report component	检测限 Limit of detection	参考文献 Reference
汞Hg（II）	MerR/MerR	-	全细胞平台	mCherry	0.1 nmol/L	[33]
			全细胞平台	GFP	4.4 nmol/L	[24]
			全细胞平台	RFP	1 mg/kg	[32]
			无细胞平台	3WJdB	0.5 nmol/L	[40]
			全细胞平台	sfCherry3C	2.24 µmol/L	[41]
	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
镉Cd（II）	ZntR/MerR	1Q08	全细胞平台	sGFP	35 nmol/L	[42]
			全细胞平台	eGFP	1 000 nmol/L	[43]
			全细胞平台	Lux	100 nmol/L	[44]
	MerR/MerR	-	全细胞平台	GFP	283.9 nmol/L	[24]
	MerR/MerR	-	全细胞平台	eGFP	3 µmol/L	[45]
	CadC/ArsR/SmtB	1U2W	全细胞平台	GFP	10 µg/mL	[46]
	CadR/MerR	-	全细胞平台	mCherry	0.1 µg/mL	[47]
	ZntR/MerR	1Q08	全细胞平台	GFP	5 µmol/L	[35]
砷As（III）	ArsR/ArsR/SmtB	1R23	邻近效应驱动	Lac Z	8 ppb	[48]
	ArsR/ArsR/SmtB	-	全细胞平台	GFP	0.1 µmol/L	[36]
	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
铜Cu（II）	CopR/CopY	-	全细胞平台	RFP	24.3 µmol/L	[49]
	CueR/MerR	1Q05	全细胞平台	eGFP	0.08 µmol/L	[50]
	CusR	-	全细胞平台	GFP	12 µmol/L	[36]
锌Zn（II）	SmtB/ArsR/SmtB	1R23	全细胞平台	eGFP	1 µmol/L	[51]
	ZntR/MerR	1Q08	全细胞平台	GFP、mCherry	5 mg/L	[52]
	MerRZntR/MerR	-	全细胞平台	eGFP、mCherry	10 µg/mL	[53]
	MerRZntR/MerR	-	全细胞平台	Lux	0.03 mmol/L	[54]
铅Pb（II）	CadR/MerR	-	全细胞平台	GFP、RFP	0.01 µg/mL	[34]
	MerR/MerR	-	全细胞平台	GFP	39.6 nmol/L	[24]
	PbrR/MerR	-	全细胞平台	靛蓝合成酶Indigoidine synthetase	0.065 mol/L	[55]
			无细胞平台	3WJdB	0.1 nmol/L	[40]
			全细胞平台	比色法	2.93 nmol/L	[56]
锑Sb（III）	ArsR/ArsR/SmtB	1R23	全细胞平台	eGFP	0.25 µmol/L	[57]
镍Ni（II）	RcnR/CsoR-RcnR	-	全细胞平台	Lux	80 nmol/L	[37]

芳香族化合物 Aromatic compound	转录因子/家族 TFs/families	PDB	反应平台 Reaction platform	报告元件 Report component	检测限 Limit of detection	参考文献 Reference
苯甲酸	BenR/XylS-AraC	-	无细胞平台	sfGFP	1 µmol/L	[65]
		-	无细胞平台	GFP	21 702.8 nmol/L	[66]
苯	DmpR/XylR-NtrC	5KBE	体外酶放大系统	ATP酶	0.3 ppm	[67]
氯苯酚	DmpR/XylR-NtrC		全细胞平台	Lac Z	100 µmol/L	[68]
苯并芘	DmpR/XylR-NtrC		全细胞平台	eGFP	2.5 ppb	[60]
甲苯	XylR/XylR-NtrC	4FE4	全细胞平台	荧光素酶	1 µmol/L	[69]
2,4-二硝基甲苯	XylR/XylR-NtrC		全细胞平台	GFP/lux	~µmol/L	[70]
	XylRv17/XylR-NtrC	-	全细胞平台	荧光素酶/lacZ	-	[71]
2-羟基-3',4'-二氯联苯	HbpR/XylR-NtrC	-	全细胞平台	荧光素酶	10 nmol/L	[72]
苯酚	MopR/XylR-NtrC	5KBE	全细胞平台	荧光素酶	1 ppb	[63]
4-硝基苯酚	Dm01/Dm12/XylR-NtrC	-	全细胞平台	RFP	10 µmol/L	[26]
水杨酸	SAR2349/NahR-LysR	4EM0	无细胞平台	3WJdB荧光适配体/sfGFP	~µmol/L	[18]
苯并芘	SalR/NahR-LysR	-	全细胞平台	荧光素酶	0.01 µmol/L	[62]
萘	NahR/NahR-LysR	-	全细胞平台	荧光素酶	50 nmol/L	[73]
水杨酸	CmeR/TetR	-	全细胞平台	eGFP	~µmol/L	[74]
苯扎氯氨	QacR/TetR/CamR	1JT0	无细胞平台	3WJdB荧光适配体	~µmol/L	[18]
苯甲酸盐	MarR/MarR	1JGS	全细胞平台	yEGFP	~ fmol/L	[75]
苯甲醛	BldR/MarR	3F3X	全细胞平台	eGFP	~µmol/L	[76]
3-羟基苯甲酸	MobR/MarR	-	无细胞平台	3WJdB荧光适配体/	-	[18]
苯亚胂酸盐	ArsR/ArsR	6J05	全细胞平台	GFP	1 µmol/L	[77]
丙酮酸盐	PdhR/GntR	-	全细胞平台	yEGFP	~ fmol/L	[75]

芳香族化合物 Aromatic compound	转录因子/家族 TFs/families	PDB	反应平台 Reaction platform	报告元件 Report component	检测限 Limit of detection	参考文献 Reference
苯甲酸	BenR/XylS-AraC	-	无细胞平台	sfGFP	1 µmol/L	[65]
		-	无细胞平台	GFP	21 702.8 nmol/L	[66]
苯	DmpR/XylR-NtrC	5KBE	体外酶放大系统	ATP酶	0.3 ppm	[67]
氯苯酚	DmpR/XylR-NtrC		全细胞平台	Lac Z	100 µmol/L	[68]
苯并芘	DmpR/XylR-NtrC		全细胞平台	eGFP	2.5 ppb	[60]
甲苯	XylR/XylR-NtrC	4FE4	全细胞平台	荧光素酶	1 µmol/L	[69]
2,4-二硝基甲苯	XylR/XylR-NtrC		全细胞平台	GFP/lux	~µmol/L	[70]
	XylRv17/XylR-NtrC	-	全细胞平台	荧光素酶/lacZ	-	[71]
2-羟基-3',4'-二氯联苯	HbpR/XylR-NtrC	-	全细胞平台	荧光素酶	10 nmol/L	[72]
苯酚	MopR/XylR-NtrC	5KBE	全细胞平台	荧光素酶	1 ppb	[63]
4-硝基苯酚	Dm01/Dm12/XylR-NtrC	-	全细胞平台	RFP	10 µmol/L	[26]
水杨酸	SAR2349/NahR-LysR	4EM0	无细胞平台	3WJdB荧光适配体/sfGFP	~µmol/L	[18]
苯并芘	SalR/NahR-LysR	-	全细胞平台	荧光素酶	0.01 µmol/L	[62]
萘	NahR/NahR-LysR	-	全细胞平台	荧光素酶	50 nmol/L	[73]
水杨酸	CmeR/TetR	-	全细胞平台	eGFP	~µmol/L	[74]
苯扎氯氨	QacR/TetR/CamR	1JT0	无细胞平台	3WJdB荧光适配体	~µmol/L	[18]
苯甲酸盐	MarR/MarR	1JGS	全细胞平台	yEGFP	~ fmol/L	[75]
苯甲醛	BldR/MarR	3F3X	全细胞平台	eGFP	~µmol/L	[76]
3-羟基苯甲酸	MobR/MarR	-	无细胞平台	3WJdB荧光适配体/	-	[18]
苯亚胂酸盐	ArsR/ArsR	6J05	全细胞平台	GFP	1 µmol/L	[77]
丙酮酸盐	PdhR/GntR	-	全细胞平台	yEGFP	~ fmol/L	[75]

抗生素 Antibiotic	转录因子/家族 TFs/Families	PDB	反应平台 Reaction platform	报告元件 Report component	检测限 Limit of detection	参考文献 Reference
四环素	TetR/TetR	1QPI	限制性内切酶	荧光探针	25 nmol/L	[85]
			全细胞平台	EGFP和mCherry	0.1 ng/mL	[86]
			aTF-NAST	RPA	0.005 nmol/L	[11]
			无细胞平台	荧光适配体	~125 nmol/L	[18]
			无细胞平台	G-四链体	18.08 ng/mL	[87]
			无细胞平台	荧光适配体	10 nmol/L	[88]
			无细胞平台	CRISPR-Cas12a	-	[89]
			无细胞平台	荧光素酶	45 nmol/L	[81]
脱水四环素			QD-FRET	光致发光	6 nmol/L	[80]
			QD-FRET	光致发光	80 nmol/L	[90]
强力霉素			全细胞平台	yEmRFP	0.3 µg/mL	[91]
			无细胞平台	荧光适配体	~0.2 µmol/L	[18]
放线菌素	ActR/TetR	3B6C	全细胞平台	-		[92]
金霉素	MphR/MphR	3FRQ	无细胞平台	荧光适配体	~125 nmol/L	[18]
放线菌素			全细胞平台	GFP	-	[93]
红霉素			全细胞平台	GFP	13 nmol/L	[83]
			无细胞平台	荧光适配体	~2.5 µmol/L	[18]
			无细胞平台	荧光素酶	7.3 nmol/L	[81]
罗红霉素			无细胞平台	荧光适配体	~2.5 µmol/L	[18]
阿奇霉素			荧光适配体	荧光适配体	~2.5 µmol/L	[18]
叠氮红霉素			全细胞平台	荧光素酶	-	[94]
竹桃霉素			全细胞平台	荧光素酶	-	[94]
苦霉素			全细胞平台	荧光素酶	-	[94]
克拉霉素	MphR/MphR	6U18	全细胞平台	GFP	1 µmol/L	[95]
			无细胞平台	荧光适配体	~2.5 µmol/L	[18]
土霉素	CtcS/MarR		无细胞平台	荧光适配体	~125 nmol/L	[18]
美罗培南	AmpR/LysR		全细胞平台	mCherry	8 pg/mL	[96]
亚胺培南			全细胞平台	mCherry	40 pg/mL	[96]