合成生物学 ›› 2021, Vol. 2 ›› Issue (5): 764-777.DOI: 10.12211/2096-8280.2021-057
周正富1, 庞雨1, 张维1, 王劲1, 燕永亮1, 郑迎迎2,3, 陈敏4, 廖志华4, 林敏1,4
收稿日期:
2021-05-07
修回日期:
2021-07-30
出版日期:
2021-10-31
发布日期:
2021-11-19
通讯作者:
林敏
作者简介:
基金资助:
Zhengfu ZHOU1, Yu PANG1, Wei ZHANG1, Jin WANG1, Yongliang YAN1, Yingying ZHENG2,3, Min CHEN4, Zhihua LIAO4, Min LIN1,4
Received:
2021-05-07
Revised:
2021-07-30
Online:
2021-10-31
Published:
2021-11-19
Contact:
Min LIN
摘要:
乳蛋白是天然动物奶的主要成分,具有高营养、易吸收、增强免疫力、抗氧化等多种生物活性。采用基因工程和细胞工厂等技术手段,高效表达天然奶中的各种乳蛋白组分,已成为当前人造奶生物合成的研发热点和技术难点。人造奶作为一个已商业化面向市场并正在改变世界的新兴科技食品,营养风味与天然牛奶相当,但不含乳糖、胆固醇、抗生素和致敏原等不良因子,其生产过程无需养殖动物,可以有效节约资源与能源,是一种颠覆传统养殖业的未来乳制品生产新模式,将引领未来食品产业和细胞农业发展方向。本文系统总结了模式微生物底盘改造、重组乳蛋白高效表达和人造奶制品产业化等相关核心技术的知识产权保护现状,探讨了目前人造奶制品研发面临的瓶颈技术挑战和生物安全评价等热点问题,介绍了乳蛋白组合表达、风味物质添加、致敏原删除和细胞工厂智造等最新发展动态,为人造奶等未来合成食品产业化提供重要的理论与技术参考。目前我国乳蛋白重组表达与人造奶生物合成技术研发力量相对薄弱,研发资金与风险投资不足。为应对日趋激烈的国际竞争,“十四五”期间我国应加大研发投入,着力突破共性关键技术与产品生产工艺,同时加快制定未来合成食品商业化管理法规与产业政策,为促进我国未来养殖业发展和实现农业碳达峰、碳中和目标提供的科技支撑。
中图分类号:
周正富, 庞雨, 张维, 王劲, 燕永亮, 郑迎迎, 陈敏, 廖志华, 林敏. 乳蛋白重组表达与人造奶生物合成:全球专利分析与技术发展趋势[J]. 合成生物学, 2021, 2(5): 764-777.
Zhengfu ZHOU, Yu PANG, Wei ZHANG, Jin WANG, Yongliang YAN, Yingying ZHENG, Min CHEN, Zhihua LIAO, Min LIN. Recombinant expression of milk proteins and biosynthesis of animal-free milk: analysis on related patents and trend for technology development[J]. Synthetic Biology Journal, 2021, 2(5): 764-777.
1 | 张超. 中国保持乳制品进口大国地位[N]. 中国食品报, 2019-09-17(4). |
ZHANG Chao. China maintains its position as a major importer of dairy products[N]. China Food Newspaper, 2019-09-17(4). | |
2 | LUCEY J A, OTTER D, HORNE D S. A 100-Year Review: Progress on the chemistry of milk and its components[J]. Journal of Dairy Science, 2017, 100(12): 9916-9932. |
3 | AUGUSTIN M A, UDABAGE P. Influence of processing on functionality of milk and dairy proteins[J]. Advances in Food and Nutrition Research, 2007, 53: 1-38. |
4 | SOPHIA T, KOSTAS D, KOSTAS N P. Cow's milk[J]. Allergenicity, 2014, 14(1):16-26. |
5 | 顾梅琪, 那立欣, 王力强. 国内外乳及乳制品食品安全问题及监督管理现状[J]. 管理观察, 2020(21): 92-94. |
GU Meiqi, NA Lixin, WANG Liqiang. Domestic and foreign milk and dairy products food safety issues and supervision status[J]. Management Observer, 2020(21):92-94 | |
6 | SALTER A M. Improving the sustainability of global meat and milk production[J]. Proceedings of the Nutrition Society, 2016, 76(1): 22-27. |
7 | 沈金荣, 史梦珂, 邓泽元, 等. 大豆复合植物蛋白饮料配方优化及其理化性质[J]. 食品工业科技, 2018, 39(2): 175-181. |
SHEN J R, SHI M K, DEND Z Y, et al. Formulation optimization and physicochemical properties of soybean compound plant protein beverage[J]. Science and Technology of Food Industry, 2018, 39(2): 175-181. | |
8 | THOMPSON P, KAPLAN D. Encyclopedia of food and agricultural ethics[M]. Dordrecht: Springer, 2018. |
9 | 陈坚. 中国食品科技:从2020到2035[J].中国食品学报, 2019, 19(12): 1-5. |
CHEN Jian. Food science and technology in China: from 2020 to 2035[J]. Journal of Chinese Institute of Food Science and Technology, 2019, 19(12): 1-5. | |
10 | BELTRÁN-BARRIENTOS L M, HERNÁNDEZ-MENDOZA A, TORRES-LLANEZ M J, et al. Fermented milk as antihypertensive functional food[J]. Journal of Dairy Science, 2016, 99: 4099-4110. |
11 | 人造牛奶有望在未来问世[J].中国乳业, 2014(7): 74. |
Artificial milk is expected to be introduced in the future[J]. China Dairy, 2014(7): 74 | |
12 | FARRELL H M, MALIN E L, BROWN E M, et al. Casein micelle structure: what can be learned from milk synthesis and structural biology?[J]. Current Opinion in Colloid & Interface Science, 2006, 11(2/3): 135-147. |
13 | KORHONEN H J. Bioactive components in bovine milk[M]. Wiley‐Blackwell, 2009. |
14 | IMAFIDON G I, FARKYE N Y, SPANIER A M. Isolation, purification, and alteration of some functional groups of major milk proteins: a review[J]. Critical Reviews in Food Science and Nutrition, 1997, 37(7): 663-689. |
15 | BAUMAN D E, MATHER I H, WALL R J, et al. Major advances associated with the biosynthesis of milk[J]. Journal of Dairy Science, 2006, 89(4): 1235-1243. |
16 | HANSSON L, BERGSTRÖM S, HERNELL O, et al. Expression of human milk beta-casein in Escherichia coli: comparison of recombinant protein with native isoforms[J]. Protein Expression and Purification, 1993, 4(5): 373-381. |
17 | LÖNNERDAL B, RIGO J, ZIEGLER E E. Recombinant human milk proteins[J]. Nestlé Nutrition Workshop, 2006, 58(58): 207. |
18 | IDIRIS A, TOHDA H, KUMAGAI H, et al. Engineering of protein secretion in yeast: strategies and impact on protein production[J]. Applied Microbiology and Biotechnology, 2010, 86(2): 403-417. |
19 | GODA S K, AQEL Y W ABU, AL-ASWAD M R, et al. Production of synthetic methionine-free and synthetic methionine-limited alpha casein: protein foodstuff for patients with homocystinuria due to cystathionine beta-synthase deficiency[J]. The Protein Journal, 2010, 29(1): 44-49. |
20 | PARK Y W. Rheological characteristics of goat and sheep milk[J]. Small Ruminant Research, 2007, 68(1/2): 73-87. |
21 | 张健, 刘晓军, 李柱刚, 等. 一种利用基因工程技术改良植物营养品质的方法: CN1544641A[P]. 2004-11-10. |
ZHANG Jian, LIU Xiaojun, LI Zhugang, et al. A method for improving the nutritional quality of plants using genetic engineering technology: CN1544641A[P]. 2004-11-10. | |
22 | WITTE B, OBLOJ P, KOKTENTURK S, et al. Food for thought: the protein transformation[R]. Boston Consulting Group. 2021-03-24. https://web-assets.bcg.com/a0/28/4295860343c6a2a5b9f4e3436114/bcg-food-for-thought-the-protein-transformation-mar-2021.pdf |
23 | 农业农村部市场预警专家委员会. 中国农业展望报告(2021—2030)[M]. 北京: 中国农业科学技术出版社, 2021. |
Professional Committee of Market Early Warning, Ministry of Agriculture and Rural Affairs,PRC. China agriculture outlook report (2021—2030)[M]. Beijing: China Agricultural Science and Technology Press, 2021. | |
24 | 林敏, 周正富, 燕永亮, 等. 一种高效降解羽毛并合成人工血红素蛋白的基因模块及应用: CN112501164A[P]. 2021-03-16. |
LIN Min, ZHOU Zhengfu, YAN Yongliang, et al. A gene module for efficient degradation of feathers and synthesis of artificial heme protein and the uses thereof: CN112501164A[P]. 2021-03-16. | |
25 | 张齐, 崔金明, 蒙海林, 等. 7种牛奶蛋白基因在大肠杆菌中的异源表达[J]. 集成技术, 2016, 5(6): 79-84. |
ZHANG Q, CUI J M, MENG H L, et al. Synthesis of seven milk proteins in Escherichia coli[J]. Journal of Integration Technology, 2016, 5(6): 79-84. | |
26 | 林敏, 周正富, 燕永亮, 等. 提高重组牛奶蛋白异源表达效率的氨基酸序列: CN112481286A[P]. 2021-03-12. |
LIN Min, ZHOU Zhengfu, YAN Yongliang, et al. Amino acid sequences to improve the efficiency of heterologous expression of recombinant milk proteins: CN112481286A[P]. 2021-03-12. | |
27 | PANDYA R, GANDHI P, JI S W, et al. Compositions comprising a casein and methods of producing the same: US10595545[P]. 2020-03-24. |
28 | GEISTLINGER T, JHALA R, KRUEGER K P, et al. Food products comprising milk proteins and non-animal proteins, and methods of producing the same: US20190216106[P]. 2019-07-18. |
29 | GEISTLINGER T. Recombinant components and compositions for use in food products: WO2020081789A9[P]. 2019-10-1. |
30 | MÅNSSON H L. Fatty acids in bovine milk fat[J]. Food & Nutrition Research, 2008, 52: 1821. |
31 | VALENTIN W, LIZ S. Cellular agriculture: an extension of common production methods for food[R]. The Good Food Institute, 2018-03-6. https://www.gfi.org/images/uploads/2018/03/Cellular-Agriculture-for-Animal-Protein.pdf. |
32 | VOIGT C A. Synthetic biology 2020-2030: six commercially-available products that are changing our world[J]. Nature Communications, 2020, 11(1): 6379. |
33 | DESHPANDE N, WILKINS M R, PACKER N, et al. Protein glycosylation pathways in filamentous fungi[J]. Glycobiology, 2008, 18(8): 626-637. |
34 | VILLA C, COSTA J, OLIVEIRA M B P P, et al. Bovine milk allergens: a comprehensive review[J]. Comprehensive Reviews in Food Science and Food Safety, 2018, 17(1): 137-164. |
35 | LEHRER S B, BANNON G A. Risks of allergic reactions to biotech proteins in foods: perception and reality[J]. Allergy, 2015, 60(5):559-564. |
36 | 郭明璋, 许文涛, 罗云波, 等. 中国食物过敏原数据库的建立与应用[J]. 食品安全质量检测学报, 2014, 5(9): 2951-2955. |
GUO M Z, XU W T, LUO Y B, et al. Establishment and application of Chinese food allergen database[J]. Journal of Food Safety & Quality, 2014, 5(9): 2951-2955. | |
37 | KANEKANIAN A. The health benefits of bioactive compounds from milk and dairy products[M]. John Wiley & Sons, Ltd., 2014. |
38 | ROELL M S, ZURBRIGGEN M D. The impact of synthetic biology for future agriculture and nutrition[J]. Current Opinion in Biotechnology, 2020, 61: 102-109. |
39 | SUN L C, XIN F J, ALPER H S. Bio-synthesis of food additives and colorants-a growing trend in future food[J]. Biotechnology Advances, 2021, 47: 107694. |
40 | TRUMP B D. Synthetic biology regulation and governance: Lessons from TAPIC for the United States, European Union, and Singapore[J]. Health Policy, 2017, 121(11): 1139-1146. |
41 | TRUMP B D, GALAITSI S E, APPLETON E, et al. Building biosecurity for synthetic biology[J]. Molecular Systems Biology, 2020, 16(7): e9723. |
42 | 杜立, 王萌. 合成生物学技术制造食品的商业化法律规范[J]. 合成生物学, 2020, 1(5): 593-608. |
DU L, WANG M. The legal issues about commercialization of food products employing synthetic biology strategies[J]. Synthetic Biology Journal, 2020, 1(5): 593-608. | |
43 | European Food Safety Authority. Outcome of the public consultation on the draft scientific opinion on the evaluation of existing guidelines for their adequacy for the microbial characterisation and environmental risk assessment of micro-organisms obtained through synthetic biology[R]. EFSA Supporting publication 2020:EN-1934. doi:10.2903/sp.efsa.2020.EN-1934. |
44 | 李德茂, 曾艳, 周桔, 等. 生物制造食品原料市场准入政策比较及对我国的建议[J]. 中国科学院院刊, 2020, 35(8): 1041-1052. |
LI D M, ZENG Y, ZHOU J, et al. Regulation and guidance for marketing of food ingredients from biomanufacturing and policy suggestions for China[J]. Bulletin of the Chinese Academy of Sciences, 2020, 35(8): 1041-1052. | |
45 | 刘晓, 熊燕, 王方, 等. 合成生物学伦理、法律与社会问题探讨[J]. 生命科学, 2012, 24(11): 1334-1338. |
LIU Xiao, XIONG Yan, WANG Fang, et al. Ethical, legal and social issues (ELSI) of synthetic biology[J]. Chinese Bulletin of Life Sciences, 2012, 24(11): 1334-1338. | |
46 | KAEBNICK G E, GUSMANO M K, MURRAY T H. The ethics of synthetic biology: next steps and prior questions[J]. Hastings Center Report, 2014, 44(S5): S4. |
47 | 欧亚昆, 雷瑞鹏. 合成生物学自我管治的伦理探析[J]. 伦理学研究, 2018(2): 53-58. |
Yakun OU, LEI Ruipeng. An ethical exploration of self-governance in synthetic biology[J]. Studies in Ethics, 2018(2): 53-58. | |
48 | 张先恩. 中国合成生物学发展回顾与展望[J]. 中国科学:生命科学, 2019, 49(12): 1543-1572. |
ZHANG X-E. Synthetic biology in China: Review and prospects[J]. SCIENTIA SINICA Vitae, 2019, 49(12): 1543-1572. | |
49 | MOUAT M J, PRINCE R. Cultured meat and cowless milk: on making markets for animal-free food[J]. Journal of Cultural Economy, 2018, 11(4): 315-329. |
50 | STEPHENS D N, DUNSFORD I, SILVIO L D, et al. Bringing cultured meat to market: Technical, socio-political, and regulatory challenges in cellular agriculture[J]. Trends in Food Science & Technology, 2018, 78(8): 155-166. |
51 | 林敏. 转基因技术[M].北京: 中国农业科学技术出版社. 2020 |
LIN Min. Transgenic technology[M]. Beijing: China Agricultural Science and Technology Press, 2020 | |
52 | STEPHENS N, ELLIS M. Cellular agriculture in the UK: a review[J]. Wellcome Open Research, 2020, 5:12. |
53 | RISCHER H, SZILVAY G R, OKSMAN-CALDENTEY K M. Cellular agriculture-industrial biotechnology for food and materials[J]. Current Opinion in Biotechnology, 2020, 61: 128-134. |
54 | MATTICK C S. Cellular agriculture: the coming revolution in food production[J]. Bulletin of the Atomic Scientists, 2018, 74(1): 32-35. |
55 | SEXTON A E, GARNETT T, LORIMER J. Framing the future of food: the contested promises of alternative proteins[J]. Environment and Planning E, Nature and Space, 2019, 2(1): 47-72. |
56 | SPRINGMANN M, CLARK M, MASON-D'CROZ D, et al. Options for keeping the food system within environmental limits[J]. Nature, 2018, 562: 519-525 |
57 | LÜ X Q, WU Y K, GONG M Y, et al. Synthetic biology for future food: research progress and future directions[J]. Future Foods, 2021, 3: 100025. |
[1] | 马雪璟, 郭畅, 华兆琳, 侯百东. 合成生物技术助力纳米颗粒疫苗理性设计时代的到来[J]. 合成生物学, 2023, (): 1-16. |
[2] | 郭肖杰, 剪兴金, 王立言, 张翀, 邢新会. 合成生物学表型测试生物反应器及其装备化研究进展[J]. 合成生物学, 2023, (): 1-21. |
[3] | 叶精勤, 黄文华, 潘超, 朱力, 王恒樑. 合成生物学在多糖结合疫苗研发中的应用[J]. 合成生物学, 2023, (): 1-15. |
[4] | 刘宽庆, 张以恒. 木质素的生物降解和生物利用[J]. 合成生物学, 2023, (): 1-14. |
[5] | 司同, 邢新会. 合成生物学装备:颠覆生命科技的利器[J]. 合成生物学, 2023, 4(5): 853-856. |
[6] | 赵国淼, 杨鑫, 张媛, 王靖, 谭剑, 魏超, 周娜娜, 李凡, 王小艳. 生物设施平台及其工业应用[J]. 合成生物学, 2023, 4(5): 892-903. |
[7] | 孙梦楚, 陆亮宇, 申晓林, 孙新晓, 王佳, 袁其朋. 基于荧光检测的高通量筛选技术和装备助力细胞工厂构建[J]. 合成生物学, 2023, 4(5): 947-965. |
[8] | 卢挥, 张芳丽, 黄磊. 合成生物学自动化装置iBioFoundry的构建与应用[J]. 合成生物学, 2023, 4(5): 877-891. |
[9] | 白仲虎, 任和, 聂简琪, 孙杨. 高通量平行发酵技术的发展与应用[J]. 合成生物学, 2023, 4(5): 904-915. |
[10] | 秦伟彤, 杨广宇. 微液滴高通量筛选方法的研究与应用进展[J]. 合成生物学, 2023, 4(5): 966-979. |
[11] | 胡哲辉, 徐娟, 卞光凯. 自动化高通量技术在天然产物生物合成中的应用[J]. 合成生物学, 2023, 4(5): 932-946. |
[12] | 张志强, 张扬, 邱维宝, 郑海荣. 超声移液及微量移液技术进展和展望[J]. 合成生物学, 2023, 4(5): 916-931. |
[13] | 刘欢, 崔球. 原位电离质谱技术在微生物菌株筛选中的应用进展[J]. 合成生物学, 2023, 4(5): 980-999. |
[14] | 陈永灿, 司同, 张建志. 自动化合成生物技术在DNA组装与微生物底盘操作中的应用[J]. 合成生物学, 2023, 4(5): 857-876. |
[15] | 肖艳, 刘亚君, 冯银刚, 崔球. 热纤梭菌在生物质能源开发中的合成生物学研究进展[J]. 合成生物学, 2023, (): 1-26. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||