Advances in Engineering Yeast Chassis for Producing Aromatic Compounds

doi:10.13523/j.cb.2204049

China Biotechnology

2022, Vol. 42

Issue (10): 80-92 DOI: 10.13523/j.cb.2204049

Advances in Engineering Yeast Chassis for Producing Aromatic Compounds

Hui-min LI,Bin JIA,Xia LI,Duo LIU^**(

)

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education,School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China

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Abstract

Aromatic compounds including lots of species are in high demand and widely used in many areas. The synthesis of aromatic compounds by constructing microbial cell factories has unique advantages and industrial applications. Yeast chassis is often used to build cell factories due to its clear genetic background, well-performed gene manipulation tools, and mature industrial system. A series of advances has been made in the production of aromatic compounds by engineering yeast chassis, and several feasible solutions have been proposed to solve key problems. In view of the strategies and challenges of yeast synthesis of aromatic compounds, this paper systematically reviews and elaborates on the five aspects, namely, the aromatic compound synthetic pathway modification, utilization of diverse carbon sources and modification of transport systems, genome multi-target modification, special yeast chassis and microbial consortium construction, and applications of synthetic biology high-throughput technologies, and provides ideas for the construction and engineering of yeast chassis for producing aromatic compounds.

Key words： Aromatic compounds Yeast Chassis engineering Genome rearrangement Synthetic biology

Received: 21 April 2022 Published: 04 November 2022

ZTFLH:

Q819

Corresponding Authors: Duo LIU E-mail: duo_liu0@tju.edu.cn

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Cite this article:

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

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2204049 OR https://manu60.magtech.com.cn/biotech/Y2022/V42/I10/80

Fig.1 Advances in yeast chassis engineering strategy for producing aromatic compounds (a)Synthetic pathway modification. ARO3:Phospho-2-dehydro-3-deoxyheptonate aldolase;ARO4: Phospho-2-dehydro-3-deoxyheptonate aldolase;ARO1:Pentafunctional AROM polypeptide;ARO7:Chorismate mutase; E4P:Erythrose 4-phosphate;PEP: Phosphoenolpyruvate;DAHP: 3-Deoxy-D-arabino-heptulosonate-7-phosphate;SHIK: Shikimic;CHA: Chorismate;PPA: Prephenic acid;SA: Salicylic acid;MA: Muconic acid;2-PE: 2-Phenylethanol (b)Utilization of diverse carbon source substrates and modification of transport systems for the synthesis of aromatic compounds (c)Genome multi-target engineering:Application of CRISPR/Cas9;Genome rearrangement (d)Non-model yeast chassis and the consortium consisting of E.coli and yeast cells for producing aromatic compounds (e)Applications of high-throughput technologies:Machine learning;Biosensors;Automated methods and platforms

产品	代谢工程策略	发酵方式	产量	文献
酪醇	敲除PDC1、PHA2;表达ARO4^K229L、ARO7^G141S、ARO3^K222L;过表达RKI1和TKL1	摇瓶	702.30 mg/L	[7]
		5 L发酵罐	9.90 g/L
酪醇	表达EcAROG^D146N、EcpheA^fbr、EcydiB、EcAROL;过表达TKL1、ARO10;敲除ARO9	摇瓶	541 mg/L	[11]
红景天苷	敲除PDC1、PHA2;表达ARO4^K229L、ARO7^G141S、RrU8GT33^opt、ARO3^K222L;过表达RKI1和TKL1	摇瓶	1 575.45 mg/L	[7]
		5 L发酵罐	26.55 g/L
莽草酸	过表达ARO1^D920A、ARO4^K229L、TKL1	摇瓶	358 mg/L	[8]
对香豆酸	过表达ARO4^K229L、ARO7^G141S、FjTAL、EcAROL;敲除ARO10、PDC5	发酵罐	1.93 g/L	[10]
对香豆酸	表达AtPAL2、AtC4H、AtATR2、CYB5、FjTAL、EcAROL、MtPDH1;过表达ARO4^K229L、ARO7^G141S;敲除PDC5、ARO10	发酵罐	12.5 g/L	[5]
对香豆酸	解脂耶氏酵母:敲除YlPYK、YlTYR1、YlTRP2、YlTRP3、YlARO8、YlARO9;过表达ScARO4^K229L、AROG^S180F、BbXFPK、AcXPK等	摇瓶	593 mg/L	[52]
2-苯乙醇	表达EcAROG^D146N、EcpheA^fbr、EcydiB、EcAROL;过表达TKL1、ARO10;敲除ARO9	摇瓶	643 mg/L	[11]
2-苯乙醇	过表达GLN3改造转运系统	摇瓶	3.59 g/L	[31]
产品	代谢工程策略	发酵方式	产量	文献
2-苯乙醇	过表达GAP1、ARO8、ARO10、ADH2、GDH2	5 L发酵罐	6.3 g/L	[32]
2-苯乙醇	解脂耶氏酵母:过表达YlPAR4、YlARO10、YlARO7、YlPHA2、ScARO7^G141S、ScARO4^K229L、AROG^S180F、BbXFPK、AcXPK等;敲除YlTYR1、YlTRP2、YlTRP3、YlARO8、YlARO9、YlPYK	摇瓶	2 426 mg/L	[52]
黏糠酸	敲除ARO3、ARO4、ZWF1;过表达ARO4^K229L、EcL_01944^opt、Pa5_5120^opt、CaHQD2^opt、TKL1;生物传感器、定向进化、ARO1截短表达	摇瓶	500 mg/L	[14]
		发酵罐	2.1 g/L
柚皮素	敲除ARO3、ARO10、PDC5、PDC6;表达ARO4^G226S;过表达AtPAL1、CoC4H、CoCPR1、AtCHI1、AtCHS3、CoCHS3、At4CL3、CoTAL1	2 L发酵罐	112 mg/L	[16]
柚皮素	解脂耶氏酵母:过表达RtTAL、Pc4CL、PhCHS、MsCHI、GhF3'H、CrCPR、SlF3H、YlARO1、YlACC1、YlACS2;培养条件优化	摇瓶	252 mg/L	[51]
圣草酚	表达Pc4CL、PhCHS、MsCHI、AmF3H、AtFLS	摇瓶	134.2 mg/L
花旗松素	表达Pc4CL、PhCHS、MsCHI、AmF3H、AtFLS、PhFMO、CrCPR	摇瓶	110.5 mg/L
天竺葵素-3- O-葡萄糖苷	表达HaCHS、MsCHI、At4CL2、AtPAL2、AmC4H、ScCPR1、PhANS、MdF3H、AaDFR、DcA3GT	深孔板	0.85 mg/L	[18]
花青素-3- O-葡萄糖苷	表达HaCHS、MsCHI、At4CL2、AtPAL2、AmC4H、ScCPR1、PhANS、MdF3H、PhF3'H、PtDFR、AtCPR1、FaA3GT2	深孔板	1.55 mg/L
飞燕草素-3- O-葡萄糖苷	表达HaCHS、MsCHI、At4CL2、AtPAL2、AmC4H、ScCPR1、PhANS、SlF3'5'H、MdF3H、IhDFR、AtCPR1、FaA3GT2	深孔板	1.86 mg/L
咖啡酸	表达PaHpaB、SeHpaC、RtTAL	摇瓶	289 mg/L	[19]
咖啡酸	敲除ARO10、PDC5;表达ARO7^fbr、ARO4^fbr、CoTAL、CoC3H、CoCPR1	摇瓶	11.432 mg/L	[20]
咖啡酸	敲除ARO10、PDC5、gpp1;过表达ScARO7^G141S、ARO4^K229L、EcAROL、FjTAL、SbPAL1、AtCPR1、PtrC4H2、PtrC4H1、PtrC3H3、PaHpaB、SeHpaC、ScARO3、ScTAL1、ScTKL1、CkPTA、LmXFPK、ScPHA2、MtPDH1、BiFADS、BsRIBBA等	摇瓶	1.6 g/L	[21]
		发酵罐	5.5 g/L
阿魏酸	敲除ARO10、PDC5、gpp1;过表达ScARO7^G141S、ARO4^K229L、EcAROL、FjTAL、SbPAL1、AtCPR1、PtrC4H2、PtrC4H1、PtrC3H3、PaHpaB、SeHpaC、ScARO3、ScTAL1、ScTKL1、CkPTA、LmXFPK、NtCOMT1、ScMET6、LiMETK1、ScADO1、ScSAH1等	摇瓶	0.42 g/L
		发酵罐	3.8 g/L
番茄枝碱	表达BvCYP76AD1、PsNCS、6OMT、CNMT、4'OMT、NMCH	摇瓶	80.6 μg/L	[22]
对氨基苯甲酸	表达ABZ1、 ABZ2、ARO4^K229L;敲除ARO7、TRP3	发酵罐	215 mg/L	[27]
原儿茶酸	敲除ADH6、ADH7、BDH2、FDC、MHT1、SAM4;表达4CL、Ppech、vdh、pobA、PdvanA、PdvanB、ligM;过表达MET6、Rdmetf1	摇瓶	810 mg/L	[28]
姜黄素	敲除fdc1;过表达PpFerA、ClDCS、ClCURS	摇瓶	2.7 mg/L	[30]
多巴胺	CYP76AD1^{W13L, F309L}	摇瓶	10.8 mg/L	[67]
紫色杆菌素	SCRaMbLE-in	摇瓶	17.5 mg/L	[48]
紫色杆菌素	解脂耶氏酵母:过表达ScARO4^K229L、AROG^S180F、BbXFPK、AcXPK等;敲除YlTYR1、YlTRP2、YlTRP3、YlARO8、YlARO9、YlPYK	摇瓶	366 mg/L	[52]
脱氧紫色杆菌素		摇瓶	55 mg/L
白藜芦醇	过表达ARO4^K229L、ScARO7^G141S、ScAcc1^S659A、 S1157A、HaTAL、At4CL1、VvVST1	摇瓶	415.65 mg/L 或531.41 mg/L	[9]
白藜芦醇	表达AtPAL2、AtC4H、At4CL2、VvVST1	摇瓶	151.65 mg/L	[29]
白藜芦醇	解脂耶氏酵母;过表达FjTAL、At4CL1、VvVST1、YlARO4^K221L、YlARO7^G139S;敲除PDC5	发酵罐	12.4 g/L	[54]

Table 1 Strategies used in engineering yeast chassis for producing aromatic compounds


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