Plant synthetic biology: new opportunities for large-scale culture of plant cells

doi:10.12211/2096-8280.2024-095

Synthetic Biology Journal ›› 2025, Vol. 6 ›› Issue (5): 1107-1125.DOI: 10.12211/2096-8280.2024-095

• Invited Review • Previous Articles Next Articles

Plant synthetic biology: new opportunities for large-scale culture of plant cells

YAN Zhaotao¹^,², ZHOU Pengfei³, WANG Yangzhong⁴, ZHANG Xin⁴, XIE Wenyan⁴, TIAN Chenfei¹^,⁴, WANG Yong¹

^1.Key Laboratory of Synthetic Biology，CAS Center for Excellence in Molecular Plant Sciences，Institute of Plant Physiology and Ecology，Chinese Academy of Sciences，Shanghai 200032，China
^2.University of Chinese Academy of Sciences，Beijing 100049，China
^3.School of Basic Medical Sciences，Guangdong Medical University，Dongguan 523808，Guangdong，China
^4.Key Laboratory of Cigarette Smoke in Tobacco Industry，Shanghai Tobacco Group Co. ，Ltd，Shanghai 201315，China

Received:2024-12-18 Revised:2025-02-24 Online:2025-11-05 Published:2025-10-31
Contact: TIAN Chenfei, WANG Yong

植物合成生物学：植物细胞大规模培养的新机遇

颜钊涛¹^,², 周鹏飞³, 汪阳忠⁴, 张鑫⁴, 谢雯燕⁴, 田晨菲¹^,⁴, 王勇¹

^1.中国科学院分子植物科学卓越创新中心，植物生理生态研究所，中国科学院合成生物学重点实验室，上海 200032
^2.中国科学院大学，北京 100049
^3.广东医科大学基础医学院，广东东莞 523808
^4.上海烟草集团有限责任公司烟草行业卷烟烟气重点实验室，上海 201315

通讯作者: 田晨菲,王勇
作者简介:颜钊涛（1998—），男，硕士研究生。主要研究方向为植物合成生物学及植物细胞培养。E-mail：yanzhaotao@cemps.ac.cn
田晨菲（1995—），女，博士后。研究方向为植物合成生物学。E-mail：tianchenfei@cemps.ac.cn
王勇（1974—），男，研究员，博士生导师。研究方向为天然产物合成生物学，通过解析天然产物的生物合成途径，运用合成生物学的思想和方法，基于工程化的设计和建构，改进复杂天然产物的生物合成效率和其生产方式，开发天然的或非天然的复杂天然产物活性成分。E-mail：yongwang@cemps.ac.cn
基金资助:
国家重点研发计划(SQ2024YFA1700126);上海市市级重大专项(24HC2820400);上海烟草集团有限责任公司行业卷烟烟气重点实验室开放性课题(K2023-1-044P)

Abstract

Abstract:

Plant Cell Culture (PCC) has emerged as a highly promising chassis for synthetic biology, offering a range of advantages such as short growth cycles, cost-effectiveness, absence of pathogenic risks, and abundant secondary metabolites. These features make PCC an attractive alternative for applications in medicine, food, and health. However, insufficient production efficiency due to difficulties in genetic transformation, complex regulatory networks, cell aggregation, and poor genetic stability remains a major obstacle that limits the commercialization of PCC. Synthetic biology, with its bottom-up engineering design approach, provides a powerful toolkit to address these challenges. By enabling the precise design and modification of native plant cells, synthetic biology offers innovative strategies to develop efficient and economically viable plant cell factories. In this paper, we first review the current status of PCC in synthesizing high-value compounds, particularly recombinant proteins and secondary metabolites. Recent advancements have demonstrated the potential of PCC to produce therapeutic proteins, vaccines, industrial enzymes and bioactive compounds such as alkaloids, flavonoids, and terpenoids. These successes underscore the versatility of PCC as a bioproduction platform. We then explore the role of synthetic biology in advancing PCC industrialization. Key developments include the creation of high-quality plant cell lines through genome editing tools like CRISPR/Cas9, enhancing genetic stability and metabolic efficiency. Additionally, synthetic biology has improved genetic transformation systems, overcoming a critical bottleneck in PCC. Enhanced expression systems, incorporating synthetic promoters and regulatory elements, have significantly boosted target compound yields. Furthermore, synthetic biology has expanded PCC applications by enabling the biosynthesis of heterologous compounds beyond their native metabolic pathways. Finally, we discuss future prospects, emphasizing the potential of synthetic biology to overcome current technical challenges. Emerging technologies including multi-omics integration, machine learning, and synthetic organelle development are anticipated to further enhance PCC’s scalability and efficiency. By addressing these challenges, synthetic biology will pave the way for large-scale plant cell cultivation, thereby facilitating its widespread adoption in industrial bioproduction. The convergence of PCC and synthetic biology holds immense potential for the sustainable, cost-effective, and scalable production of high-value compounds.

Key words: plant synthetic biology, plant cells, biosynthesis, natural product, genetic engineering

摘要：

植物细胞培养（plant cell culture， PCC）作为一种极具发展潜力的生物合成平台，具有生长周期短、成本效益高、无病原危害、次生代谢产物丰富等优势，在医药、食品和保健等领域备受关注。然而，生产效率不足是限制PCC应用于商业化生产的最大阻碍，其中，遗传转化效率低、调控网络复杂、细胞结团及遗传稳定性差是主要困难。合成生物学遵循自下而上的工程化建造理念，对天然植物细胞进行精准设计与改造，为开发高效、经济可行的植物细胞工厂提供了新的解决方案。本文回顾了PCC作为合成平台在生产重组蛋白和次生代谢产物中的研究现状。重点探讨了植物合成生物学对PCC在工业化发展中的推动作用，包括优质植物细胞系的构建、遗传转化体系的优化、表达系统的优化、生产效率与产能的提升以及赋予植物细胞合成异源产物的能力。未来，PCC的发展更需强调合成生物学理念和技术在突破当前技术瓶颈中的关键作用，以促进植物细胞大规模培养的进一步发展。

关键词: 植物合成生物学, 植物细胞, 生物合成, 天然产物, 基因工程

CLC Number:

YAN Zhaotao, ZHOU Pengfei, WANG Yangzhong, ZHANG Xin, XIE Wenyan, TIAN Chenfei, WANG Yong. Plant synthetic biology: new opportunities for large-scale culture of plant cells[J]. Synthetic Biology Journal, 2025, 6(5): 1107-1125.

颜钊涛, 周鹏飞, 汪阳忠, 张鑫, 谢雯燕, 田晨菲, 王勇. 植物合成生物学：植物细胞大规模培养的新机遇[J]. 合成生物学, 2025, 6(5): 1107-1125.

Figures/Tables 6

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产品	物种	应用	制造商	参考资料
紫杉醇	Taxus chinensis L.	药物，抗癌	Phyton Biotech	https://phytonbiotech.com/about-pcf/
迷迭香酸	Melissa axillaris L.	药物，抗氧化	Aethera Biotech	https://www.aetherabiotech.it/en/
可可粉	Theobroma cacao L.	食品成分	California Cultured	https://www.cacultured.com/
黄烷醇	Theobroma cacao L.	医药、保健品成分	AyanaBio	http://www.ayanabio.com
海茴香细胞提取物	Crithmummaritimum L.	化妆品成分，抗氧化	Ancelbio	http://ancelbio.cn/
火绒草细胞提取物	Leontopodium alpinum L.	化妆品成分，抗皱	Ancelbio	http://ancelbio.cn/
GBL-Skin¹	Glycyrrhizauralensis L.	化妆品原料，乳化剂	Green Bioactives	https://greenbioactives.com/
白藜芦醇	Graptoveria amethorum L.	化妆品、保健品成分	Bioharvest Science	https://bioharvest.com/
Elelyso	Daucus carota L.	戈谢病治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
OPRX-100	Daucus carota L.	溃疡性结肠炎治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
PRX-102	Nicotiana tabacum L.	法布里病治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
新城疫疫苗	Nicotiana tabacum L.	新城疫疫苗	Dow AgroSciences	https://www.dow.com/
MOSS-FH	Physcomitriumpatens L.	溶血性尿毒症综合征治疗性蛋白	Greenovation Biotech GmbH	http://www.greenovation.com/ developmental-pipeline.html

产品	物种	应用	制造商	参考资料
紫杉醇	Taxus chinensis L.	药物，抗癌	Phyton Biotech	https://phytonbiotech.com/about-pcf/
迷迭香酸	Melissa axillaris L.	药物，抗氧化	Aethera Biotech	https://www.aetherabiotech.it/en/
可可粉	Theobroma cacao L.	食品成分	California Cultured	https://www.cacultured.com/
黄烷醇	Theobroma cacao L.	医药、保健品成分	AyanaBio	http://www.ayanabio.com
海茴香细胞提取物	Crithmummaritimum L.	化妆品成分，抗氧化	Ancelbio	http://ancelbio.cn/
火绒草细胞提取物	Leontopodium alpinum L.	化妆品成分，抗皱	Ancelbio	http://ancelbio.cn/
GBL-Skin¹	Glycyrrhizauralensis L.	化妆品原料，乳化剂	Green Bioactives	https://greenbioactives.com/
白藜芦醇	Graptoveria amethorum L.	化妆品、保健品成分	Bioharvest Science	https://bioharvest.com/
Elelyso	Daucus carota L.	戈谢病治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
OPRX-100	Daucus carota L.	溃疡性结肠炎治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
PRX-102	Nicotiana tabacum L.	法布里病治疗性蛋白	Protalix BioThera	http://protalix.comhttps://clinicaltrials.gov
新城疫疫苗	Nicotiana tabacum L.	新城疫疫苗	Dow AgroSciences	https://www.dow.com/
MOSS-FH	Physcomitriumpatens L.	溶血性尿毒症综合征治疗性蛋白	Greenovation Biotech GmbH	http://www.greenovation.com/ developmental-pipeline.html

植物物种	拉丁名	蛋白名称	细胞材料	产量	参考文献
水稻	Oryza sativa L.	人骨形态发生蛋白2(BMP2)	水稻愈伤组织细胞	21.5 μg/mL培养液	[33]
水稻	Oryza sativa L.	人类生长激素(hGH)	水稻愈伤组织细胞	57 mg/L培养液	[34]
水稻	Oryza sativa L.	合成牛胰蛋白酶原(synthetic bovine trypsinogen)	水稻愈伤组织细胞	15 mg/L培养液	[35]
水稻	Oryza sativa L.	酸性葡萄糖苷酶(GAA)	水稻愈伤组织细胞	37 mg/L培养液	[36]
水稻	Oryza sativa L.	血管内皮生长因子(VEGF)	水稻愈伤组织细胞	19 mg/L培养液	[37]
水稻	Oryza sativa L.	包膜糖蛋白(envelope glycoprotein)	水稻愈伤组织细胞	18.5 μg/g	[38]
水稻	Oryza sativa L.	贝伐单抗(Bevacizumab monoclonal antibody)	水稻愈伤组织细胞	160.7～242.8 mg/kg	[39]
烟草	Nicotiana tabacum L.	人抗胰蛋白酶(human α1-antitrypsin)	BY-2悬浮细胞	34.7 mg/L培养液	[40]
烟草	Nicotiana tabacum L.	人生长激素(human growth hormone)	BY-2悬浮细胞	5.2%总可溶蛋白	[41]

植物物种	拉丁名	蛋白名称	细胞材料	产量	参考文献
水稻	Oryza sativa L.	人骨形态发生蛋白2(BMP2)	水稻愈伤组织细胞	21.5 μg/mL培养液	[33]
水稻	Oryza sativa L.	人类生长激素(hGH)	水稻愈伤组织细胞	57 mg/L培养液	[34]
水稻	Oryza sativa L.	合成牛胰蛋白酶原(synthetic bovine trypsinogen)	水稻愈伤组织细胞	15 mg/L培养液	[35]
水稻	Oryza sativa L.	酸性葡萄糖苷酶(GAA)	水稻愈伤组织细胞	37 mg/L培养液	[36]
水稻	Oryza sativa L.	血管内皮生长因子(VEGF)	水稻愈伤组织细胞	19 mg/L培养液	[37]
水稻	Oryza sativa L.	包膜糖蛋白(envelope glycoprotein)	水稻愈伤组织细胞	18.5 μg/g	[38]
水稻	Oryza sativa L.	贝伐单抗(Bevacizumab monoclonal antibody)	水稻愈伤组织细胞	160.7～242.8 mg/kg	[39]
烟草	Nicotiana tabacum L.	人抗胰蛋白酶(human α1-antitrypsin)	BY-2悬浮细胞	34.7 mg/L培养液	[40]
烟草	Nicotiana tabacum L.	人生长激素(human growth hormone)	BY-2悬浮细胞	5.2%总可溶蛋白	[41]

物种	外植体部位	类型	激素	培养基	周期	参考文献
水稻	胚乳	愈伤组织	1.0 mg/L 2,4-D； 1.0 mg/L 6BA	N6培养基	6个月	[3]
葡萄	叶片	愈伤组织	0.05 mg/L NAA； 0.5 mg/L 2,4-D； 2.0 mg/L KT	B5培养基	21天	[21]
胡萝卜	茎段	愈伤组织	0.5 mg/L 2,4-D	MS培养基	14天	[54]
红豆杉	胚乳	愈伤组织	1.0 mg/L 2,4-D； 0.5 mg/L 6BA	B5培养基	15天	[4]
人参	根部	愈伤组织	1.0 mg/L 2,4-D； 0.1 mg/L KT	MS培养基	90天	[5]
地黄	根部	形成层干细胞	2.0 mg/L NAA； 2.0 mg/L 6BA	MS培养基	14天	[29]

Plant synthetic biology: new opportunities for large-scale culture of plant cells

植物合成生物学：植物细胞大规模培养的新机遇

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植物物种		改造策略	细胞材料	化合物类别	作用效果	参考文献
山葡萄	Vitis amurensis Rupr.	过表达VaCPK29	悬浮细胞	多酚类	白藜芦醇1.39 mg/L培养液	[106]
柑橘	Citrusreticulata L.	过表达CsMADS6、PSY、PDS和CCD1	愈伤组织细胞	类胡萝卜素	类胡萝卜素23 µg/g DW	[102]
加州藜芦	Veratrum californicum var.	过表达VnOSC1	愈伤组织细胞	生物碱	环巴胺6.14 mg/g DW	[91]
红豆杉	Taxus baccata L.	过表达NINV	悬浮细胞	二萜类	紫杉醇94 μg/g FW	[107]
红豆杉	Taxus baccata L.	过表达BAPT、DBTNBT	悬浮细胞	二萜类	紫杉醇310 mg/L培养液	[90]
灌木状辣椒	Capsicum frutescens L.	过表达VpVAN	悬浮细胞	芳香族化合物	香兰素(573.39±120.70) µg/g组织	[108]
烟草	Nicotiana tabacum L.	过表达转录因子AmRos1和AmDel	BY-2悬浮细胞	黄酮类	花青素30 mg/g DW	[98]
甜菜	Beta vulgaris L.	过表达VpVAN	毛状根	芳香族化合物	香兰素(0.0430 ±0.003) mg/g DW	[109]
烟草	Nicotiana tabacum L.	过表达HCHL	悬浮细胞	黄酮类	花青素(75.4±6.1) µmol/g FW	[110]
竹	Phyllostachys nigra L.	过表达PpHCH	悬浮细胞	酚类	4-羟基苯甲醇1.7 g/L培养液	[111]
烟草	Nicotiana tabacum L.	过表达CqCYP76AD1、CqDODA、CqCDOPA5GT和CqAmaSy	BY-2悬浮细胞	苷类	苋菜苷(13.67±4.13) µmol/L；甜菜苷(26.60±1.53) µmol/L	[112]
烟草	Nicotiana tabacum L.	过表达CqCYP76AD1-1和CqDODA-1	BY-2悬浮细胞	类黄酮	甜菜苷(19.53±8.60) µmol/L	[112]
烟草	Nicotiana tabacum L.	过表达VoGES	悬浮细胞	单萜类	香叶醇16 µg/g DW	[103]
烟草	Nicotiana tabacum L.	过表达PgDDS	悬浮细胞	三萜类	达玛烯二醇-Ⅱ 573 µg/g DW	[113]
烟草	Nicotiana tabacum L.	过表达PgDDS和CYP716A47	悬浮细胞	三萜类	原人参二醇980.9 µg/g DW	[104]
烟草	Nicotiana tabacum L.	CRISPRi抑制NtC4H	悬浮细胞	苯丙素类	绿原酸1799.69 ng/mL培养液；乔松酮384.19 ng/mL培养液；柚皮素597.53 ng/mL培养液	[95]
水稻	Oryza sativa L.	修饰近靶顺式作用元件，激活PHYTOENE SYNTHASE 1启动子	愈伤组织细胞	类胡萝卜素	八氢番茄红素7.13 µg/g DW	[114]
水飞蓟	Silybum marianum L.	过表达STS	悬浮细胞	多酚类	白藜芦醇50 ng/g FW	[115]
连翘	Forsythia koreana L.	过表达CYP81Q1；RNAi抑制UGT71A18和PLR	悬浮细胞	木质素	芝麻素(10.83±0.35) µg/g DW	[105]

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