胞内生物传感器提高微生物细胞工厂的精细调控

doi:10.11949/0438-1157.20211164

摘要/Abstract

摘要：

在当今倡导化合物绿色制造的背景下，利用微生物细胞工厂合成新化合物或提高化合物的产量是绿色化工技术发展的重要方向之一。但目标化合物的低产是微生物细胞工厂合成的常见问题。解决这个瓶颈的有效方法之一是在微生物细胞中设计生物传感器来监测和调控化合物的生物合成。详细介绍了胞内生物传感器的种类和作用机制，重点阐释了生物传感器如何与微生物细胞工厂中产物合成途径设计相结合，从而提高细胞工厂的精细调控和目标产物的合成能力。最后还讨论了目前胞内生物传感器设计所面临的挑战和可行的解决方案。

关键词: 胞内生物传感器, 微生物细胞工厂, 精细调控, 绿色生物制造, 合成生物学

Abstract:

Under the background of advocating the green manufacturing of compounds, the use of microbial cell factories to synthesize new compounds or increase the yield of compounds is one of the important directions for the development of green chemical technology. However, the low yield of target compounds is a common problem in the synthesis of microbial cell factories. One of the effective ways to solve this bottleneck is to design biosensors in microbial cells to monitor and regulate the biosynthesis of compounds. This paper introduces the types and mechanism of intracellular biosensors in details, focusing on how biosensors are coupled with the design of product synthesis pathways in microbial cell factories to improve the fine regulation of cell factories and the ability to synthesize target products. Finally, the challenges and feasible solutions of the current intracellular biosensor design are discussed.

Key words: intracellular biosensor, microbial cell factory, fine regulation, green biological manufacturing, synthetic biology

中图分类号:

Q 819

孙怡, 张腾, 吕波, 李春. 胞内生物传感器提高微生物细胞工厂的精细调控[J]. 化工学报, 2022, 73(2): 521-534.

Yi SUN, Teng ZHANG, Bo LYU, Chun LI. Improvement for fine regulation of microbial cell factory by intracellular biosensors[J]. CIESC Journal, 2022, 73(2): 521-534.

图/表 8

参考文献 102

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胞内生物传感器的关键元件			响应因子	微生物细胞宿主	文献
转录调节元件	启动子	gadE, rstA	法尼基焦磷酸	大肠杆菌	[30]
		hmgA	尿黑酸	铜绿假单胞菌	[31]
		araBAD	脱氧紫色杆菌素	大肠杆菌	[32]
		srfA	细胞密度	枯草芽孢杆菌	[33]
		gas	衣康酸	黑曲霉	[34]
		hsp12, hsp26	高温，乙酸	酿酒酵母	[35]
	转录因子	FapR	丙二酰辅酶A	酿酒酵母	[36]
		Lrp	L-缬氨酸	谷氨酸棒杆菌	[37]
		AgaR	L-精氨酸	钝齿棒杆菌	[38]
		Saro-0803	白藜芦醇	大肠杆菌	[39]
翻译调节元件	核糖体开关	茶碱RNA适体	茶碱	大肠杆菌	[40]
		菠菜RNA适体	硫胺素5′-焦磷酸, S-腺苷-同型半胱氨酸	大肠杆菌	[41-43]
		荧光RNA适体	胍	大肠杆菌	[44]
蛋白质	G蛋白偶联受体		丁香酚、香豆素、二氢茉莉酮和苯乙酮	酿酒酵母	[45]
	双组分系统		苹果酸	大肠杆菌	[46]
	F?rster共振能量转移系统		L-2-羟基戊二酸	恶臭假单胞菌	[47]
	酶偶联		l-3,4-二羟基苯丙氨酸	酿酒酵母	[48]
			木糖	酿酒酵母	[49]
			乳酸	大肠杆菌	[49]

胞内生物传感器的关键元件			响应因子	微生物细胞宿主	文献
转录调节元件	启动子	gadE, rstA	法尼基焦磷酸	大肠杆菌	[30]
		hmgA	尿黑酸	铜绿假单胞菌	[31]
		araBAD	脱氧紫色杆菌素	大肠杆菌	[32]
		srfA	细胞密度	枯草芽孢杆菌	[33]
		gas	衣康酸	黑曲霉	[34]
		hsp12, hsp26	高温，乙酸	酿酒酵母	[35]
	转录因子	FapR	丙二酰辅酶A	酿酒酵母	[36]
		Lrp	L-缬氨酸	谷氨酸棒杆菌	[37]
		AgaR	L-精氨酸	钝齿棒杆菌	[38]
		Saro-0803	白藜芦醇	大肠杆菌	[39]
翻译调节元件	核糖体开关	茶碱RNA适体	茶碱	大肠杆菌	[40]
		菠菜RNA适体	硫胺素5′-焦磷酸, S-腺苷-同型半胱氨酸	大肠杆菌	[41-43]
		荧光RNA适体	胍	大肠杆菌	[44]
蛋白质	G蛋白偶联受体		丁香酚、香豆素、二氢茉莉酮和苯乙酮	酿酒酵母	[45]
	双组分系统		苹果酸	大肠杆菌	[46]
	F?rster共振能量转移系统		L-2-羟基戊二酸	恶臭假单胞菌	[47]
	酶偶联		l-3,4-二羟基苯丙氨酸	酿酒酵母	[48]
			木糖	酿酒酵母	[49]
			乳酸	大肠杆菌	[49]

胞内生物传感器类型	关键元件	应用目的	目标化合物	微生物细胞宿主	文献
基于转录因子	ChnR	高通量筛选优良菌株	内酰胺	大肠杆菌	[69]
基于转录因子	FapR	高通量筛选优良菌株	丙二酰辅酶A	大肠杆菌	[20]
基于转录因子	XylR	高通量筛选优良菌株	木糖	酿酒酵母	[70]
基于转录因子	SoxR	高通量筛选优良菌株	NADPH	大肠杆菌	[54]
基于转录因子	C4-lysR	高通量筛选优良菌株	3-羟基丙酸	大肠杆菌	[71]
核糖体开关	glmS	高通量筛选优良菌株	乙酰神经氨酸	大肠杆菌	[72]
核糖体开关	锤头状核酶	高通量筛选优良菌株	新霉素	酿酒酵母	[73]
核糖体开关	色氨酸RNA适体	高通量筛选优良菌株	色氨酸	大肠杆菌	[74]
核糖体开关	glmS	高通量筛选优良菌株	N-乙酰氨基葡萄糖	酿酒酵母	[75]
基于转录因子	FadR	动态调控代谢平衡	香草酸	大肠杆菌	[76]
基于转录因子	IpsA	动态调控代谢平衡	D-葡萄糖二酸	大肠杆菌	[21]
基于蛋白质	双组分系统	动态调控代谢平衡	α-法尼烯	酿酒酵母	[77]
基于转录因子	LuxR,TetR	动态调控代谢平衡	酪醇，红景天苷	大肠杆菌	[78]
基于启动子	AraC_mev	动态调控代谢平衡	甲羟戊酸	大肠杆菌	[79]
基于转录因子	FedR，PadR	动态调控代谢平衡	柚皮素	大肠杆菌	[80]

胞内生物传感器类型	关键元件	应用目的	目标化合物	微生物细胞宿主	文献
基于转录因子	ChnR	高通量筛选优良菌株	内酰胺	大肠杆菌	[69]
基于转录因子	FapR	高通量筛选优良菌株	丙二酰辅酶A	大肠杆菌	[20]
基于转录因子	XylR	高通量筛选优良菌株	木糖	酿酒酵母	[70]
基于转录因子	SoxR	高通量筛选优良菌株	NADPH	大肠杆菌	[54]
基于转录因子	C4-lysR	高通量筛选优良菌株	3-羟基丙酸	大肠杆菌	[71]
核糖体开关	glmS	高通量筛选优良菌株	乙酰神经氨酸	大肠杆菌	[72]
核糖体开关	锤头状核酶	高通量筛选优良菌株	新霉素	酿酒酵母	[73]
核糖体开关	色氨酸RNA适体	高通量筛选优良菌株	色氨酸	大肠杆菌	[74]
核糖体开关	glmS	高通量筛选优良菌株	N-乙酰氨基葡萄糖	酿酒酵母	[75]
基于转录因子	FadR	动态调控代谢平衡	香草酸	大肠杆菌	[76]
基于转录因子	IpsA	动态调控代谢平衡	D-葡萄糖二酸	大肠杆菌	[21]
基于蛋白质	双组分系统	动态调控代谢平衡	α-法尼烯	酿酒酵母	[77]
基于转录因子	LuxR,TetR	动态调控代谢平衡	酪醇，红景天苷	大肠杆菌	[78]
基于启动子	AraC_mev	动态调控代谢平衡	甲羟戊酸	大肠杆菌	[79]
基于转录因子	FedR，PadR	动态调控代谢平衡	柚皮素	大肠杆菌	[80]

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