合成生物系统构建与绿色生物“智”造

doi:10.11949/0438-1157.20200516

摘要/Abstract

摘要：

微生物细胞工厂生产化学品是解决能源和环境问题的有效方式之一。越来越多的化合物可通过合成生物系统实现在微生物中的合成，但菌株的生产能力和鲁棒性仍需进一步提高。提高细胞工厂的智能化，实现生物“智”造过程，将是解决菌株发酵生产能力不足和鲁棒性差的重要途径。本文从蛋白质设计的智能化、生物传感器的智能化、代谢调控的智能化、菌株进化的智能化以及发酵过程智能化等五个层面对生物“智”造的研究现状进行介绍。生物“智”造的发展将为提高工业生物过程的生产水平和过程节能减排做出重要贡献。

关键词: 生物工程, 分子生物学, 合成生物学, 智能化, 生物制造, 鲁棒性, 生物传感器, 基因线路

Abstract:

The production of chemicals in microbial cell factories is one of the effective ways to solve energy and environmental problems. Many chemical products have been produced by synthetic biology, but production ability and robustness of the strains still needs to been improved. Development of intelligent cell factory and realizing intelligent biological manufacturing is an important approach to improve the production and robustness. This review introduces the research status of intelligent biological manufacturing from five following aspects: protein design, biosensor, metabolism regulation, strain evolution and fermentation process. The development of biological “intelligence” will make an important contribution to improving the production level of industrial biological processes and process energy saving and emission reduction.

Key words: biological engineering, molecular biology, synthetic biology, intelligence, biological manufacturing, robustness, biosensor, genetic circuit

中图分类号:

Q 75

秦磊, 俞杰, 宁小钰, 孙文涛, 李春. 合成生物系统构建与绿色生物“智”造[J]. 化工学报, 2020, 71(9): 3979-3994.

Lei QIN, Jie YU, Xiaoyu NING, Wentao SUN, Chun LI. Synthetic biological system construction and green intelligent biological manufacturing[J]. CIESC Journal, 2020, 71(9): 3979-3994.

图/表 8

图1 生物“智”造包括的主要内容

Fig.1 The brief contents of intelligent biological manufacturing

图2 蛋白质变构调节的从头设计（a） pH诱导的α-螺旋同源三聚体的解离[26]；（b）基于α-螺旋的蛋白质开关[30]Fig.2 De novo design of tunable conformational changes of proteins

(a) pH-induced dissociation of α-helix homotrimer[26]; (b) α-helix based protein switch[30]

图3 酶催化的智能化（a）利用酶的杂泛性合成不同产物[35]；（b）通过调节温度改变酶的性质[36]

Fig.3 Intelligence of enzymes(a) synthesis of various products by enzyme promiscuity[35]; (b) changing properties of enzymes by regulating temperature[36]

图4 转录调节元件作为生物传感器（a）感应IPP的转录调节元件的理性设计[53]；（b）低温诱导表达系统[59]；（c）大肠杆菌中光诱导和光抑制表达系统[64]；（d）酿酒酵母中光诱导表达系统[65]

Fig.4 Transcription regulatory elements as biosensors(a) rational design of IPP-response element[53]; (b) cold-induced expression system[59]; (c) light-induced and light-repressed expression system inE. coli[64]; (d) light-induced expression system in S. cerevisiae[65]

图5 自主动态调控策略（a） FPP反馈抑制与反馈诱导提高紫穗槐二烯产量[56]；（b）麦角固醇反馈抑制降低竞争途径通量[91]；（c）转录负担诱导的CRISPRi反馈调节[92]；（d）胁迫诱导的抗胁迫反馈调节[57]；（e）二次酸感应细胞死亡系统[93]

Fig.5 Autonomous dynamic regulations(a) FPP feedback inhibition and induction increase amorphadiene production[56]; (b) ergosterol feedback inhibition decreases competitive pathway flux[91]; (c) burden induced CRISPRi feedback regulation[92]; (d) stress-driven feedback regulation of anti-stress system[57]; (e) two count pH sensitive kill switch[93]

图6 基于生物传感器的智能自主进化策略（a） FREP[53]；（b） AEMS[39]；（c）利用pH感应的核糖体开关的自主进化[73]

Fig.6 Intelligent autonomous evolutions(a) FREP[53]; (b) AEMS[39]; (c) autonomous evolution based on pH-sensitive riboswitch[73]

图7 SCRaMbLE作用原理

Fig.7 Mechanism of SCRaMbLE

图8 发酵工厂的智能化

Fig.8 Intelligence of fermentation control

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