生物技术进展 ›› 2023, Vol. 13 ›› Issue (1): 65-71.DOI: 10.19586/j.2095-2341.2022.0156
收稿日期:
2022-09-01
接受日期:
2022-10-11
出版日期:
2023-01-25
发布日期:
2023-02-07
通讯作者:
姜凌
作者简介:
孙卉 E-mail: sunhui@caas.cn;
基金资助:
Hui SUN(), Chunyi ZHANG, Ling JIANG(
)
Received:
2022-09-01
Accepted:
2022-10-11
Online:
2023-01-25
Published:
2023-02-07
Contact:
Ling JIANG
摘要:
植物分子农场可以利用植物生产具有药物用途的重组蛋白或者次生代谢化合物,应用广泛。随着对动植物中具有药物用途的代谢途径的深入解析,代谢途径中关键限速酶或调控蛋白的功能不断被明确,如何选择植物分子农场的底盘植物和遗传改造途径等问题,特别是如何协同提高植物制药产量与品质一直是植物分子农场体系建立中面临的关键科学问题。综述了药用的植物分子农场的最新研究进展,着重介绍了底盘植物的选择与药用植物分子农场的构建策略,以期为提高分子农场应用效果提供有力的科技支撑。
中图分类号:
孙卉, 张春义, 姜凌. 药用植物分子农场研究进展[J]. 生物技术进展, 2023, 13(1): 65-71.
Hui SUN, Chunyi ZHANG, Ling JIANG. Progress of Plant Molecular Farming in Pharmaceutical Use[J]. Current Biotechnology, 2023, 13(1): 65-71.
类型 | 优点 | 缺点 |
---|---|---|
细菌 | 快速繁殖、无场所限制 | 需要诱导才能产生产物、有治疗风险、无法产生复杂产品 |
酵母 | 快速增殖、无场所限制、蛋白质产量高 | 需要诱导才能产生产物 |
动物细胞培养 | 周期长、类人蛋白修饰、蛋白质产量高、无场所限制 | 维护和生产成本高、需要诱导才能产生产物、产生的蛋白大小有限制、有治疗风险 |
植物细胞培养 | 周期短、维护和生产成本低、蛋白质产量高 | 需要诱导才能产生产物、产生的蛋白大小有限制、聚糖修饰可能导致过敏反应 |
拟南芥 | 生物信息完整、基因组小、表达系统简单且成熟 | 不适用于商业大规模应用生产 |
紫花苜蓿和三叶草 | 产量高、用于动物疫苗、容易繁殖 | 存在过多草酸、叶片中蛋白质稳定性较低 |
烟草 | 产量高、表达系统成熟、可以快速扩大规模 | 存在有害生物碱、叶片中蛋白质稳定性较低 |
油菜和红花 | 油体纯化技术适合脂溶性产物 | 生物量低、聚糖修饰与油体积累不匹配 |
番茄 | 可食用、温室栽培 | 培育成本高、需冷藏、受季节影响 |
土豆和胡萝卜 | 可食用、特定的储藏器官 | 食用前必须煮熟、淀粉含量较高 |
豌豆、大豆和花生 | 蛋白质含量高、生产成本低 | 表达水平低 |
小麦和大麦 | 储藏期间的产物稳定、生产成本低 | 需考虑粮食作物安全问题、产量低、转化难度高 |
水稻和玉米 | 储藏期间的产物稳定、产量高、提取方便、生物信息完整、表达系统成熟易于转化、生产成本低 | 需考虑粮食作物安全问题,聚糖修饰可能导致过敏反应 |
表1 不同类型分子农场的优缺点
Table 1 Advantages and disadvantages cons of different types of molecular farms
类型 | 优点 | 缺点 |
---|---|---|
细菌 | 快速繁殖、无场所限制 | 需要诱导才能产生产物、有治疗风险、无法产生复杂产品 |
酵母 | 快速增殖、无场所限制、蛋白质产量高 | 需要诱导才能产生产物 |
动物细胞培养 | 周期长、类人蛋白修饰、蛋白质产量高、无场所限制 | 维护和生产成本高、需要诱导才能产生产物、产生的蛋白大小有限制、有治疗风险 |
植物细胞培养 | 周期短、维护和生产成本低、蛋白质产量高 | 需要诱导才能产生产物、产生的蛋白大小有限制、聚糖修饰可能导致过敏反应 |
拟南芥 | 生物信息完整、基因组小、表达系统简单且成熟 | 不适用于商业大规模应用生产 |
紫花苜蓿和三叶草 | 产量高、用于动物疫苗、容易繁殖 | 存在过多草酸、叶片中蛋白质稳定性较低 |
烟草 | 产量高、表达系统成熟、可以快速扩大规模 | 存在有害生物碱、叶片中蛋白质稳定性较低 |
油菜和红花 | 油体纯化技术适合脂溶性产物 | 生物量低、聚糖修饰与油体积累不匹配 |
番茄 | 可食用、温室栽培 | 培育成本高、需冷藏、受季节影响 |
土豆和胡萝卜 | 可食用、特定的储藏器官 | 食用前必须煮熟、淀粉含量较高 |
豌豆、大豆和花生 | 蛋白质含量高、生产成本低 | 表达水平低 |
小麦和大麦 | 储藏期间的产物稳定、生产成本低 | 需考虑粮食作物安全问题、产量低、转化难度高 |
水稻和玉米 | 储藏期间的产物稳定、产量高、提取方便、生物信息完整、表达系统成熟易于转化、生产成本低 | 需考虑粮食作物安全问题,聚糖修饰可能导致过敏反应 |
1 | FAUSTHER-BOVENDO H, KOBINGER G. Plant-made vaccines and therapeutics[J]. Science, 2021, 373(6556): 740-741. |
2 | NOGUEIRA M, ENFISSI E M, ALMEIDA J, et al.. Creating plant molecular factories for industrial and nutritional isoprenoid production[J]. Curr. Opin. Biotechnol., 2018, 49: 80-87. |
3 | YUSIBOV V, STREATFIELD S J, KUSHNIR N. Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond[J]. Hum. Vaccin., 2011, 7(3): 313-321. |
4 | PAUL M, MA J K. Plant-made pharmaceuticals: leading products and production platforms[J]. Biotechnol. Appl. Biochem., 2011, 58(1): 58-67. |
5 | FISCHER R, BUYEL J F. Molecular farming-the slope of enlightenment[J/OL]. Biotechnol. Adv., 2020, 40: 107519 [2020-01-13]. . |
6 | GRECO R, MICHEL M, GUETARD D, et al.. Production of recombinant HIV-1/HBV virus-like particles in Nicotiana tabacum and Arabidopsis thaliana plants for a bivalent plant-based vaccine[J]. Vaccine, 2007, 25(49): 8228-8240. |
7 | BOYHAN D, DANIELL H. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide[J]. Plant Biotechnol. J., 2011, 9(5): 585-598. |
8 | GOVEA-ALONSO D O, RUBIO-INFANTE N, GARCIA-HERNANDEZ A L, et al.. Immunogenic properties of a lettuce-derived C4(V3) 6 multiepitopic HIV protein[J]. Planta, 2013, 238(4): 785-792. |
9 | BISHOP B M. Potential and emerging treatment options for Ebola virus disease[J]. Ann. Pharmacother., 2015, 49(2): 196-206. |
10 | SABALZA M, VAMVAKA E, CHRISTOU P, et al.. Seeds as a production system for molecular pharming applications: status and prospects[J]. Curr. Pharm. Des., 2013, 19(31): 5543-5552. |
11 | SABALZA M, MADEIRA L, VAN DOLLEWEERD C, et al.. Functional characterization of the recombinant HIV-neutralizing monoclonal antibody 2F5 produced in maize seeds[J]. Plant Mol. Biol., 2012, 80(4-5): 477-488. |
12 | HUDSON L C, GARG R, BOST K L, et al.. Soybean seeds: a practical host for the production of functional subunit vaccines[J/OL]. Biomed. Res. Int., 2014, 2014: 340804 [2014-04-14]. . |
13 | CUNHA N B, MURAD A M, RAMOS G L, et al.. Accumulation of functional recombinant human coagulation factor IX in transgenic soybean seeds[J]. Transgenic Res., 2011, 20(4): 841-855. |
14 | WAKASA Y, TAKAIWA F. The use of rice seeds to produce human pharmaceuticals for oral therapy[J]. Biotechnol. J., 2013, 8(10): 1133-1143. |
15 | FAYE L, GOMORD V. Success stories in molecular farming-a brief overview[J]. Plant Biotechnol. J., 2010, 8(5): 525-528. |
16 | GUILLON S, TREMOUILLAUX-GUILLER J, PATI P K, et al.. Hairy root research: recent scenario and exciting prospects- commentary[J]. Curr. Opin. Plant Biol., 2006, 9(3): 341-346. |
17 | ROYCHOWDHURY D, HALDER M, JHA S. Agrobacterium rhizogenes mediated transformation in medicinal plants: genetic stability in long-term culture[M]//JHA S (ed). Transgenesis and secondary metabolism. Reference series in phytochemistry. Springer, Cham., 2016: 1-23. . |
18 | BALASUBRAMANIAN M, ANBUMEGALA M, SURENDRAN R, et al.. Elite hairy roots of Raphanus sativus (L.) as a source of antioxidants and flavonoids[J]. 3Biotech, 2018, 8(2):128. |
19 | KUNDU S, SALMA U, ALI M N, et al.. Development of transgenic hairy roots and augmentation of secondary metabolites by precursor feeding in Sphagneticola calendulacea (L.) Pruski[J]. Ind. Crop Prod., 2018, 121: 206-215. |
20 | LAN X, ZENG J, LIU K, et al.. Comparison of two hyoscyamine 6β-hydroxylases in engineering scopolamine biosynthesis in root cultures of Scopolia lurida [J]. Biochem. Biophys. Res. Commun., 2018, 497(1): 25-31. |
21 | JIAO J, GAI Q Y, WANG W, et al.. Remarkable enhancement of flavonoid production in a co-cultivation system of Isatis tinctoria L. hairy root cultures and immobilized Aspergillus niger [J]. Ind. Crop Prod., 2018, 112: 252-261. |
22 | KASTELL A, SCHREINER M, KNORR D, et al.. Influence of nutrient supply and elicitors on glucosinolate production in E. sativa hairy root cultures[J]. Plant. Cell Tissue Organ. Cult., 2018, 132(3): 561-572. |
23 | DEHGHAN E, HÄKKINEN S T, OKSMAN-CALDENTEY K M, et al.. Production of tropane alkaloids in diploid and tetraploid plants and in vitro hairy root cultures of Egyptian henbane (Hyoscyamus muticus L.)[J]. Plant Cell Tissue Organ. Cult., 2012,110(1): 35-44. |
24 | CAI Y, CHEN L, LIU X, et al.. CRISPR/Cas9-mediated genome editing in soybean hairy roots[J/OL]. PLoS ONE, 2015, 10: e0136064 [2015-08-18]. . |
25 | SUN Q Y, DING L W, LOMONOSSOFF G P, et al.. Improved expression and purification of recombinant human serum albumin from transgenic tobacco suspension culture[J]. J. Biotechnol., 2011, 155(2): 164-172. |
26 | FUENTES P, ZHOU F, ERBAN A, et al.. A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop[J/OL]. Elife, 2016, 5: e13664[2016-06-14]. . |
27 | MERCX S, SMARGIASSO N, CHAUMONT F, et al.. Inactivation of the β(1,2)-xylosyltransferase and the α(1,3)-fucosyl- transferase genes in Nicotiana tabacum BY-2 cells by a multiplex CRISPR/Cas9 strategy results in glycoproteins without plant-specific glycans[J/OL]. Front. Plant Sci., 2017, 8: 403[2017-03-27]. . |
28 | SCHILLBERG S, RAVEN N, FISCHER R, et al.. Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures[J]. Curr. Pharm. Des., 2013, 19(31): 5531-5542. |
29 | QIU X, WONG G, AUDET J, et al.. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp[J]. Nature, 2014, 514(7520): 47-53. |
30 | MOR T S. Molecular pharming's foot in the FDA's door: Protalix's trailblazing story[J]. Biotechnol. Lett., 2015, 37(11): 2147-2150. |
31 | DECKER E L, RESKI R. Glycoprotein production in moss bioreactors[J]. Plant Cell Rep. 2012, 31(3): 453-460. |
32 | RASALA B A, MUTO M, LEE P A, et al.. Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtii [J]. Plant Biotechnol. J., 2010, 8(6): 719-733. |
33 | PUJOL M, GAVILONDO J, AYALA M, et al.. Fighting cancer with plant-expressed pharmaceuticals[J]. Trends Biotechnol., 2007, 25(10): 455-459. |
34 | SHARMA A K, SHARMA M K. Plants as bioreactors: recent developments and emerging opportunities[J]. Biotechnol. Adv., 2009, 27(6): 811-832. |
35 | MOUSTAFA K, ABDULLAH M A, TRÉMOUILLAUX-GUILLER J. Molecular farming on rescue of pharma industry for next generations[J]. Crit. Rev. Biotechnol., 2016, 36(5): 840-850. |
36 | NA W, PARK N, YEOM M, et al.. Ebola outbreak in Western Africa 2014: what is going on with Ebola virus?[J] Clin. Exp. Vaccine Res., 2015, 4(1): 17-22. |
37 | HE X, GALPIN J D, TROPAK M B, et al.. Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complexglycan-deficient (cgl) plants[J]. Glycobiology, 2012, 22(4): 492-503. |
38 | WU H, SINGH N K, LOCY R D, et al.. Expression of immunogenic VP2 protein of infectious bursal disease virus in Arabidopsis thaliana [J]. Biotechnol. Lett., 2004, 26(10): 787-792. |
39 | ZHU Q, TAN J, LIU Y G. Molecular farming using transgenic rice endosperm[J]. Trends Biotechnol., 2022, 4(10):1248-1260. |
40 | WARD B J, MAKARKOV A, SÉGUIN A, et al.. Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18-64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials[J]. Lancet, 2020, 396(10261):1491-1503. |
41 | BARTA A, SOMMERGRUBER K, THOMPSON D, et al.. The expression of a nopaline synthase-human growth hormone chimaeric gene in transformed tobacco and sunflower callus tissue[J]. Plant Mol. Biol., 1986, 6(5): 347-357. |
42 | SIJMONS P C, DEKKER B M, SCHRAMMEIJER B, et al.. Production of correctly processed human serum albumin in transgenic plants[J]. Biotechnol., 1990, 8(3): 217-221. |
43 | SHAALTIEL Y, BARTFELD D, HASHMUELI S, et al.. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system[J]. Plant Biotechnol. J., 2007, 5(5): 579-590. |
44 | TECHEN N, PARVEEN I, PAN Z, et al.. DNA barcoding of medicinal plant material for identification[J]. Curr. Opin. Biotechnol., 2014, 25: 103-110. |
45 | EDWARDS D, BATLEY J. Plant genome sequencing: applications for crop improvement[J]. Plant Biotechnol. J., 2010, 8(1): 2-9. |
46 | POUVREAU B, VANHERCKE T, SINGH S. From plant metabolic engineering to plant synthetic biology: the evolution of the design/build/test/learn cycle[J]. Plant Sci., 2018, 273: 3-12. |
47 | ZHOU Z, TAN H, LI Q, et al.. CRISPR/Cas9-mediated efficient targeted mutagenesis of RAS in Salvia miltiorrhiza [J]. Phytochem., 2018, 148: 63-70. |
48 | LI B, CUI G, SHEN G, et al.. Targeted mutagenesis in the medicinal plant Salvia miltiorrhiza [J/OL]. Sci. Rep., 2017, 7: 43320 [2017-03-03]. . |
49 | KUMAR S R, SHILPASHREE H B, NAGEGOWDA D A. Terpene moiety enhancement by overexpression of geranyl (geranyl) diphosphate synthase and geraniol synthase elevates monomeric and dimeric monoterpene indole alkaloids in transgenic Catharanthus roseus [J/OL]. Front. Plant Sci., 2018, 9: 942 [2018-06-06].. |
50 | FENG S, SONG W, FU R, et al.. Application of the CRISPR/Cas9 system in Dioscorea zingiberensis [J]. Plant Cell Tissue Organ. Cult., 2018, 135:133-141. |
51 | YAO L, ZHANG H, LIU Y, et al.. Engineering of triterpene metabolism and overexpression of the lignin biosynthesis gene PAL promotes ginsenoside Rg3 accumulation in ginseng plant chassis[J]. J. Integr. Plant Biol. 2022, 64(9): 1739-1754. |
52 | DONG C, QU G, GUO J, et al.. Rational design of geranylgeranyl diphosphate synthase enhances carotenoid production and improves photosynthetic efficiency in Nicotiana tabacum [J]. Sci. Bull., 2022, 67(3): 315-327. |
53 | VALDIANI A, HANSEN O K, NIELSEN U B, et al.. Bioreactor based advances in plant tissue and cell culture: challenges and prospects[J]. Crit. Rev. Biotechnol. 2019, 39 (1): 20-34. |
54 | LEI L. Lettuce-manufactured pharmaceuticals[J]. Nat. Plants, 2019, 5(7): 646-646. |
55 | ALUKO R E. Antihypertensive peptides from food proteins[J]. Annu. Rev. Food Sci. Technol., 2015, 6: 235-262. |
56 | QIAN D, QIU B, ZHOU N, et al.. Hypotensive activity of transgenic rice seed accumulating multiple antihypertensive peptides[J]. J. Agric. Food Chem., 2020, 68(27): 7162-7168. |
57 | STOGER E, FISCHER R, MOLONEY M, et al.. Plant molecular pharming for the treatment of chronic and infectious diseases[J]. Annu. Rev. Plant Biol., 2014, 65: 743-768. |
58 | NIAZIAN M, SADAT NOORI S A, TOHIDFAR M, et al.. Essential oil yield and agro-morphological traits in some Iranian ecotypes of ajowan (Carum copticum L.)[J]. J. Essent. Oil Bear. Plants, 2017, 20(4): 1151-1156. |
59 | OBEMBE O O, POPOOLA J O, LEELAVATHI S, et al.. Advances in plant molecular farming[J]. Biotechnol. Adv., 2011, 29(2): 210-222. |
60 | FISCHER R, SCHILLBERG S, HELLWIG S, et al.. GMP issues for recombinant plant-derived pharmaceutical proteins[J]. Biotechnol. Adv., 2012, 30(2): 434-439. |
61 | BOIVIN S, KOZAK S, MEIJERS R. Optimization of protein purification and characterization using Thermofluor screens[J]. Protein Expr. Purif., 2013, 91(2): 192-206. |
62 | HUEBBERS J W, BUYEL J F. On the verge of the market-plant factories for the automated and standardized production of biopharmaceuticals[J/OL]. Biotechnol. Adv., 2021,46: 107681[2021-12-14]. . |
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