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中国生物工程杂志

China Biotechnology
China Biotechnology  2020, Vol. 40 Issue (8): 84-96    DOI: 10.13523/j.cb.2003024
    
Research Progress in Synthetic Biology of P450s in Terpenoid Synthesis
ZHANG Yu-ting1,2,LI Wei-guo1,2,LIANG Dong-mei1,2,QIAO Jian-jun1,2,CAI YIN Qing-ge-le1,2,**()
1 Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology,Tianjin University, Tianjin 300072, China
2 Syn Bio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin 300072, China
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Abstract  

The cytochrome P450 oxidase can catalyze a series of regiospecific and stereospecific chemical steps and participate in the synthesis of many natural products such as terpenoids, sterols and alkaloids. Terpenoids are a large class of compounds in active natural products and have important value in the fields of medicine and perfume. Terpenoids require P450s for biosynthesis and post-modification, but at present, the lower catalytic activity of known P450s greatly limits the efficiency of terpenoid biosynthesis. Therefore, it’s urgent to discover and modify highly active P450s for terpenoid biosynthesis to fully realize its immense industrial application potentiality. This article reviews the different P450s families in terpene metabolism and recent advances in the discovery and engineering of P450s in terpene biosynthesis. Furthermore, it highlights the main strategies of synthetic biology in broadening the application of P450s in terpene synthesis. Feasible strategies have been proposed to further accelerate the discovery of P450s and P450s engineering, based on synthetic biology technology, this article put forward suggestions and prospects for the future application of P450s in terpenoid synthesis.



Key wordsCytochrome P450      Terpenoids      Discovery of P450s      Engineering of P450s      Synthetic biology     
Received: 08 March 2020      Published: 10 September 2020
ZTFLH:  Q819  
Corresponding Authors: YIN Qing-ge-le CAI     E-mail: qinggele@tju.edu.cn
Cite this article:

ZHANG Yu-ting,LI Wei-guo,LIANG Dong-mei,QIAO Jian-jun,CAI YIN Qing-ge-le. Research Progress in Synthetic Biology of P450s in Terpenoid Synthesis. China Biotechnology, 2020, 40(8): 84-96.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2003024     OR     https://manu60.magtech.com.cn/biotech/Y2020/V40/I8/84

Fig.1 The catalytic cycle of P450s
Fig.2 Overview of the isoprenoid biosynthetic pathways Key enzymes of each pathway are shown: 1-deoxy-D-xylulose-5-phosphate synthase (DXS), 1-deoxy-D-xylulose-5-phosphate reductase(DXR), acetoacetyl-CoA thiolase (AAT), HMG-CoA synthase (HMGS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), IPP-DMAPP isomerase (IDI), geranyl diphosphate synthase (GPPS), farnesyl diphosphate synthase (FPPS), and geranylgeranyl diphosphate synthase (GGPPS), terpene synthetases (TS)
物种 P450 底物 产物或终产物 参考文献
Catharanthus roseuse CYP72A1 loganin secologanin [24]
Catharanthus roseuse CYP76B6 geraniol 10-hydroxy-geraniol [25]
Mentha CYP71D13 limonene trans-isopiperitenol [26]
Mentha CYP71D18 limonene trans-carveol [26]
Nicotiana tabacum CYP71D20 5-epi-aristolochene capsidiol [27]
Artemisia annua CYP71AV1 amorphadiene artemisinic acid [28]
Lactuca sativa CYP71BL1 germacrene A acid 6β-hydroxy-germacrene A acid [29]
Helianthus annus CYP71BL2 germacrene A acid 8β-hydroxy-germacrene A acid [29]
Picea sitchensis CYP720B4 dehydroabietadiene dehydroabietic acid [30]
Pinus taeda CYP720B1 abietadiene resin acid [31]
Arabidopsis CYP88A ent-kaurenoic acid gibberellin [32]
Avena strigosa CYP51H10 β-amyrin avenacin A-1 [34]
Medicago truncatula CYP716A12 β-amyrin、erythrodiol oleanolic acid [37]
Panax ginseng CYP716A47 dammarenediol protopanaxadiol [39]
Panax ginseng CYP716A53v2 protopanaxatriol ginsenoside saponins [40]
Glycyrrhiza CYP88D6 β-amyrin 11-oxo-β-amyrin [38]
Glycyrrhiza CYP72A154 11-oxo-β-amyrin glycyrrhetic acid [41]
Medicago truncatula CYP72A63 β-amyrin 11-deoxoglycyrrhetic acid [41]
Glycine max CYP93E1、CYP93E2、CYP93E3 β-amyrin 24-OH-β-amyrin [42]
Table1 Plant cytochrome P450s involved in the synthesis of terpenes and their derivatives
家族 亚家族 涉及的代谢功能
CYP51[34] CYP51G 参与三萜甾醇的合成
CYP51H 参与三萜皂苷的合成
CYP71[21] CYP71A、CYP71AR、CYP76B 参与单萜合成
CYP71BE、CYP76AH 参与二萜丹参酮的合成
CYP71BA、CYP71BL、CYP71Z、CYP71AV、CYP706B 参与倍半萜合成
CYP71D 参与单萜、倍半萜及二萜合成
CYP76M 参与二萜植保素的合成
CYP82G 参与萜类挥发物DMNT的合成
CYP93E 参与三萜皂苷甘草甜素的合成
CYP99A 参与二萜稻壳酮的合成
CYP701A 参与二萜赤霉素(GA)的合成
CYP705A 参与三萜合成
CYP710[33] CYP710A 参与二萜赤霉素(GA)的合成
CYP711[43] CYP711A 参与萜类信号分子独角金内酯的合成
CYP72[41] CYP72A 参与单萜吲哚类生物碱以及三萜合成
CYP72C 参与三萜油菜素内酯的合成
CYP714A 参与二萜衍生物甜菊醇的合成
CYP714D 参与二萜赤霉素(GA)的合成
CYP734A 参与三萜油菜素内酯的合成
CYP85[44] CYP85A 参与三萜油菜素内酯的合成
CYP88A 参与二萜赤霉素(GA)的合成
CYP88D 参与三萜皂苷的合成
CYP90A、CYP90B、CYP90C、CYP90D 参与三萜油菜素内酯的合成
CYP707A 参与三萜油菜素内酯的生物合成和倍半萜脱落酸(ABA)的分解代谢
CYP708A 参与三萜合成
CYP716A 参与三萜人参皂苷的合成
CYP720B 参与二萜松香酸的合成
CYP725A 参与二萜紫杉醇的合成
CYP724B 参与三萜油菜素内酯的合成
CYP97[45] CYP97A、CYP97B、CYP97C 参与四萜类胡萝卜素的合成
Table2 Distribution of functionally characterized P450s in terpenoid metabolism
Fig.3 The main strategy of P450s catalyzing the synthesis of terpenes
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