The past and present of vitamin E

doi:10.12211/2096-8280.2020-022

Abstract

Abstract:

Vitamin E, as one of the most important antioxidants in biological systems, has a variety of biological functions. For example, it can maintain normal metabolism and improve the fertility and immunity of humans and animals. It occupies an important position in the fields of medicine and feed. It is a basic supplemental product for people in China and also one of the three major vitamin products with big production volume and sale in the international market. Since it was developed in 1938, the synthesis technology of vitamin E has experienced a history of more than 80 years. With technological innovations, a relatively stable market has gradually formed for vitamin E. Here, we summarized the development of vitamin E synthesis technology, including extraction from natural resources and synthesis with chemical, biological and biochemical routes. The technologies of chemical and biochemical synthesis as the most competitive processes are introduced in details. The history of vitamin E is reviewed and the future development of vitamin E is prospected.

Key words: vitamin E, trimethylnaphthalene, isophytol, farnesene, synthetic biology

摘要：

维生素E作为人和动物体必需且最主要的抗氧化剂之一，功效广泛，可用作维持机体正常功能，提高机体生育能力、免疫能力等，在医药、饲料等领域中占有重要地位。维生素E是我国的民生基础产业产品，也是国际市场上用途非常广泛、产销量极大的三大维生素支柱产品之一，市场前景广阔。自1938年维生素E被成功合成以来，维生素E的合成技术经历了80多年的历史，随着技术的发展逐渐形成了目前比较稳定的市场格局。本文总结了维生素E合成技术一路的发展，主要包括天然提取、化学全合成、生物全合成，以及生物-化学合成等，着重介绍了主流的化学全合成技术，以及新兴产业技术——合成生物技术引领的生物-化学合成技术。回顾了维生素E的发展历史并对未来发展进行了展望。

关键词: 维生素E, 三甲基氢醌, 异植物醇, 法尼烯, 合成生物技术

CLC Number:

Q814

Tian MA, Zixin DENG, Tiangang LIU. The past and present of vitamin E[J]. Synthetic Biology Journal, 2020, 1(2): 174-186.

马田, 邓子新, 刘天罡. 维生素E的“前世”和“今生”[J]. 合成生物学, 2020, 1(2): 174-186.

Figures/Tables 8

Fig. 1 The structure of vitamin E

Fig. 2 One step condensation of trimethylhydroquinone with isophytol to produce vitamin E

Fig. 3 The main synthesis technology of trimethylhydroquinone

Fig. 4 The major synthesis technology of isophytol

Fig. 5 The biosynthesis of vitamin E

Fig. 6 Biochemical synthesis of biobased farnesene, a key intermediate in the synthesis of vitamin E

Fig. 7 Engineering E. coli to overproduce farnesene by the Targeted Metabolic Engineering system

Fig. 8 Comparison of the production of vitamin E through the 3-step synthesis using farnesene as precursor with 7-step synthesis from linalool and dihydrolinalool or citral

References 70

1	EVANS H M, BISHOP K S. On the existence of a hitherto unrecognized dietary factor essential for reproduction[J]. Science, 1922, 56(1458): 650-651.
2	KAMAL-ELDIN A, APPELQVIST L A. The chemistry and antioxidant properties of tocopherols and tocotrienols[J]. Lipids, 1996, 31(7): 671-701.
3	HOSOMI A, ARITA M, SATO Y, et al. Affinity for [alpha]-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs[J]. FEBS Letters, 1997, 409(1): 105-108.
4	REBOUL E. Vitamin E bioavailability: Mechanisms of intesti-nal absorption in the spotlight[J]. Antioxidants, 2017, 6(4): 95.
5	WEBER P, BIRRINGER M, BLUMBERG J B, et al. Vitamin E in human health [M]. New York: Humana Press, 2019: 31-41.
6	DELLAPENNA D. A decade of progress in understanding vitamin E synthesis in plants[J]. Journal of Plant Physiology, 2005, 162(7): 729-737.
7	TRABER G M. Vitamin E inadequacy in humans: causes and consequences[J]. Advances in Nutrition, 2014, 5(5): 503-514.
8	BURTON G W, INGOLD K U. Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function[J]. Accounts of Chemical Research, 1986, 19(7): 194-201.
9	EUCH-FAYACHE G E, YOSR B, RIM A, et al. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency[J]. Brain A Journal of Neurology, 2014, 137(2):402-410.
10	LEE P, ULATOWSKI L M. Vitamin E: mechanism of transport and regulation in the CNS[J]. IUBMB Life, 2019, 71(4):424-429.
11	LEWIS E D, MEYDANI S N, WU D Y. Regulatory role of vitamin E in the immune system and inflammation[J]. IUBMB Life, 2019, 71(4): 487-494.
12	SOZEN E, DEMIREL T, OZER N K. Vitamin E: regulatory role in the cardiovascular system[J]. IUBMB Life, 2019, 71(4):507-515.
13	MIYAZAWA T, BURDEOS G C, ITAYA M, et al. Vitamin E: regulatory redox interactions [J]. IUBMB Life, 2019, 71(4):430-441.
14	FARIA-SILVA C, ASCENSO A, COSTA A M, et al. Feeding the skin: a new trend in food and cosmetics convergence[J]. Trends in Food Science & Technology, 2020, 95:21-32.
15	ABRAHAM A, KATTOOR A J, SALDEEN T, et al. Vitamin E and its anticancer effects[J]. Critical Reviews in Food Science and Nutrition, 2019, 59(17):2831-2838.
16	CONSTANTINOU C, CHARALAMBOUS C, KANAKIS D. Vitamin E and cancer: an update on the emerging role of γ and δ tocotrienols[J]. European Journal of Nutrition, 2020，59:845-857.
17	CASATI M, BOCCARDI V, FERRI E, et al. Vitamin E and Alzheimer’s disease: the mediating role of cellular aging[J]. Aging Clinical and Experimental Research, 2020, 32:459-464.
18	BELLÉS M, CAMPO M DEL MAR, RONCALÉS P, et al. Supranutritional doses of vitamin E to improve lamb meat quality[J]. Meat Science, 2019, 149:14-23.
19	PONTES G C S, MONTEIRO P L J JR, PRATA A B,et al. Effect of injectable vitamin E on incidence of retained fetal membranes and reproductive performance of dairy cows[J]. Journal of Dairy Science, 2015, 98(4): 2437-2449.
20	BRIGELIUS-FLOH R. Vitamin E: the shrew waiting to be tamed[J]. Free Radical Biology and Medicine, 2009, 46(5): 543-554.
21	MCCURRY P M, TURNER S W, PICKENS C, et al. Processes for the purification of tocopherol and/or sterol compounds and compositions containing orthoborate ester mixtures: US6429320B1[P]. 2002-08-06.
22	刘云，丁霄霖，朱丹华. 超临界CO₂萃取浓缩天然维生素E的研究[J]. 化学工程, 2006, 34(4):59-62.
	LIU Y, DING X L, ZHU D H. Extraction and concentration natural vitamin E using supercritical CO₂[J]. Chemical Engineering, 2006, 34(4):59-62.
23	栾礼侠，许松林，任艳奎. 分子蒸馏技术提纯天然维生素E的工艺研究[J]. 中国粮油学报, 2006, 21(1):100-103.
	LUAN L X, XU S L, REN Y K. Refining vitamin E by short path distillation[J]. Journal of the Chinese Cereals and Oils, 2006, 21(1):100-103.
24	BINDER T P, HILALY A K. Process for production of high purity tocopherols: US6673945B2[P]. 2004-01-06.
25	武文华，曹玉平，刘凯，等. 天然维生素E提取工艺研究现状[J]. 中国油脂, 2016, 41(8): 88-91.
	WU W H, CAO Y P, LIU K, et al. Advance in extraction technology of natural vitamin E[J]. China Oils and Fats, 2016, 41(8): 88-91.
26	李禄慧，徐妙云，张兰，等. 不同作物中维生素E含量的测定和比较[J]. 中国农学通报, 2011, 27(26):124-128.
	LI L H, XU M Y, ZHANG L, et al. Determinate and analysis the content of vitamin E in different specie[J]. Chinese Agricultural Science Bulletin, 2011, 27(26):124-128.
27	DELLAPENNA D. A decade of progress in understanding vitamin E synthesis in plants[J]. Journal of Plant Physiology, 2005, 162(7): 729-737.
28	GRAFEN P, KIEFER H, JAEDICKE H. Preparation of vitamin E: US5468883A[P]. 1995-11-21.
29	OLSON G L, SAUCY G. Synthesis of vitamin E: US4243598A[P]. 1981-01-06
30	CARRIL M, ALTMANN P, BONRATH W, et al. Methyltrioxorhenium-catalysed oxidation of pseudocumene in the presence of amphiphiles for the synthesis of vitamin E[J]. Catalysis Science & Technology, 2012, 2: 722-724.
31	张天永, 刘晓思, 李彬, 等. 偶联剂改性对γ-Al₂O₃催化氧化偏三甲苯性能的影响[J]. 化学通报, 2017, 80(6): 573-578.
	ZHANG T Y, LIU X S, LI B, et al. Effect of coupling agent modification on the catalytic performance of γ-Al₂O₃ for pseudocumene oxidation[J]. Chemistry Bulletin, 2017, 80(6): 573-578.
32	白元盛，李子成，王立新，等. 2,3,5-三甲基氢醌的合成研究进展[J]. 合成化学, 2014, 22(3): 423-428.
	BAI Y S, LI Z C, WANG L X, et al. Research progress on the synthesis of 2,3,5-trimethylhydroquinone[J]. Chinese Journal of Synthetic Chemistry, 2014, 22(3): 423-428.
33	乔建成, 陈强, 蔡东伟. 一种通过4-叔丁基苯酚合成2,3,6-三甲基苯酚的工艺: CN102976902B[P]. 2013-03-20.
	QIAO J C, CHEN Q, CAI D W. Process for synthesizing2,3,6-trimethylphenol by 4-tert-butylphenol: CN102976902B[P]. 2013-03-20.
34	乔建成, 陈强, 蔡东伟. 一种通过苯酚合成2,3,6-三甲基苯酚的工艺: CN102976903B[P]. 2013-03-20.
	QIAO J C, CHEN Q, CAI D W. Process for synthesizing2,3,6-trimethylphenol by phenol: CN102976903B[P]. 2013-03-20.
35	KISHORE D, RODRIGUES A E. Liquid phase catalytic oxidation of isophorone with tert-butylhydroperoxide over Cu/Co/Fe-MgAl ternary hydrotalcites[J]. Applied Catalysis A: General, 2008, 345(1): 104-111.
36	曾庆宇, 宋文杰, 张琴, 等. 一种2,3,5-三甲基氢醌二酯的合成方法: CN102180793B[P]. 2014-08-27.
	ZENG Q Y, SONG W J, ZHANG Q, et al. Method for synthesizing2,3,5-trimethylhydroquinone diester: CN102180793B[P]. 2014-08-27.
37	KUŚTROWSKI P, SUŁKOWSKA D, CHMIELARZ L, et al. Aldol condensation of citral and acetone over mesoporous catalysts obtained by thermal and chemical activation of magnesium-aluminum hydrotalcite-like precursors[J]. Applied Catalysis A: General, 2006, 302(2): 317-324.
38	黄敏, 钟振声. 从山苍子油中提取柠檬醛的研究进展[J]. 精细化工中间体, 2003, 33(3): 13-15.
	HUANG M, ZHONG Z S. Researching progress in synthesis of citral with Litsea cubeba oil[J]. Fine Chemical Intermediates, 2003, 33(3): 13-15.
39	WEGNER G，KAIBEL G，THERE J，et al. Continuous method for producing citral: WO2008037693A1[P]. 2008-04-03.
40	LIMBACH M, TELES J H, ABDALAH R, et al. Method for isomerizing olefinically unsaturated alcohols: US20130006021A1[P]. 2013-10-22.
41	蒋淇忠, 徐俊, 马紫峰, 等. 脱氢芳樟醇合成柠檬醛[J]. 高效化学工程学报, 2002, 16(2):185-188.
	JIANG Q Z, XU J, MA Z F, et al. The synthesis of citral from dehydrolinalool[J]. Journal of Chemical Engineering of Chinese Universities, 2002, 16(2):185-188.
42	KIDO Y, KITAYAMA M, YONEDA K, et al. Process for producing 6-methylheptan-2-one: US5840992A[P]. 1998-11-24.
43	王哲，毛善俊，李浩然，等. 维生素E的催化合成路线分析[J]. 物理化学学报, 2018, 34 (6): 598-617.
	WANG Z, MAO S J, LI H R, et al. How to synthesize vitamin E[J]. Acta Physico-Chimica Sinica, 2018, 34 (6):598-617.
44	BABLER J H. Process for preparing tertiary alkynols: US5349071A[P]. 1994-09-20.
45	KIDO Y, KUMAGAI N, IWASAKI H, et al. Process for producing6-methyl-3-hepten-2-one and 6-methyl-2-heptanone analogues, and process for producing phyton or isophytol: US5955636A[P]. 1999-09-21.
46	SOLL J, SCHULTZ G. Comparison of geranylgeranyl and phytyl substituted methylquinols in the tocopherol synthesis of spinach chloroplasts[J]. Biochemical & Biophysical Research Communications, 1979, 91(3): 715-720.
47	DELLAPENNA D, POGSON B J. Vitamin synthesis in plants: tocopherols and carotenoids[J]. Annual Review of Plant Biology, 2006, 57:711-738.
48	MUNNE-BOSCH S, FALK J. New insights into the function of tocopherols in plants[J]. Planta, 2004, 218(3): 323-326.
49	DELLAPENNA D, LAST R L. Progress in the dissection and manipulation of plant vitamin E biosynthesis[J]. Physiologia Plantarum, 2006, 126(3): 356-368.
50	KONDA A R, NAZARENUS T J, NGUYEN H, et al. Metabolic engineering of soybean seeds for enhanced vitamin E tocochromanol content and effects on oil antioxidant properties in polyunsaturated fatty acid-rich germplasm[J]. Metabolic Engineering, 2020, 57: 63-73.
51	LU Y, RIJZAANI H, KARCHER D, et al. Efficient metabolic pathway engineering in transgenic tobacco and tomato plastids with synthetic multigene operons[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(8): E623-E632.
52	CAHOON E B, HALL S E, RIPP K G, et al. Metabolic redesign of vitamin E biosynthesis in plants for tocotrienol production and increased antioxidant content[J]. Nature Biotechnology, 2003, 21(9): 1082-1087.
53	RODRÍGUEZ‐ZAVALA J S, ORTIZ‐CRUZ M A, MENDOZA‐HERNÁNDEZ G, et al. Increased synthesis of α‐tocopherol, paramylon and tyrosine by Euglena gracilis under conditions of high biomass production[J]. Journal of Applied Microbiology, 2010, 109(6): 2160-2172.
54	ALBERMANN C, GHANEGAONKAR S, LEMUTH K, et al. Biosynthesis of the vitamin E compound δ‐tocotrienol in recombinant Escherichia coli cells[J]. Chembiochem, 2008, 9(15): 2524-2533.
55	于洪巍, 沈斌, 叶丽丹. 一种在酿酒酵母中表达的酶及高产α-和γ-生育三烯酚的基因工程菌及其构建方法: CN201910749343.0[P]. 2019-11-08.
56	ZHU F, ZHONG X, HU M, et al. In vitro reconstitution of mevalonate pathway and targeted engineering of farnesene overproduction in Escherichia coli[J]. Biotechnology & Bioengineering, 2014, 111(7): 1396-1405.
57	刘天罡，朱发银，邓子新. 一种生产法尼烯的菌株及其应用: CN201310209421[P]，2013-08-14.
	LIU T G，ZHU F Y，DENG Z X. Bacterial strain for producing farnesene and application of bacterial strain: CN201310209421[P]. 2013-08-14.
58	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.
59	DENG Y F，LI S，XU Q，et a1．Production of fumaric acid by simultaneous saccharification and fermentation of starchy materials with 2-deoxyglucose-resistant mutant strains of Rhizopus oryzae[J]. Bioresource Technology, 2012, 107: 363-367.
60	陈坚, 梁楠, 刘立明, 等. 一株产α-酮戊二酸重组菌的构建及用其生产α-酮戊二酸的方法: CN200810019989.5[P]. 2008-08-20.
	CHEN J, LIANG N, LIU L M, et al. Construction of bacterial strain producing alpha-oxoglutarate recombination and method for producing alpha-oxoglutarate by the same: CN200810019989.5[P]. 2008-08-20.
61	CHEN G Q, JIANG X R. Engineering microorganisms for improving polyhydroxyalkanoate biosynthesis[J]. Current Opinion in Biotechnology, 2018, 53: 20-25.
62	应汉杰，杨蕴毅，贺沁婷，等. 一株高产核酸酶P1的桔青霉菌及其选育方法: CN200710022932.6[P], 2007-11-07.
	YING H J，YANG Y Y，HE Q T，et al. Penicillium citrinum bacteria with high nuclease P1 yield and its selective breeding process: CN200710022932.6[P]. 2007-11-07.
63	应汉杰，李淑亚，陈勇，等. 一种生产尿嘧啶核苷酸的新方法: CN201010124103.0[P], 2010-08-18.
	YING H J，LI S Y，CHEN Y，et al. Novel method for producing uracil nucleotide: CN201010124103.0[P]. 2010-08-18.
64	GAO Q, TAN G Y, XIA X, et al. Learn from microbial intelligence for avermectins overproduction[J]. Current Opinion of Biotechnology, 2017, 48: 251-257.
65	郑裕国，王亚军，薛亚平，等. 一种微生物发酵制备阿卡波糖的方法: CN201010605821.X[P], 2011-08-03.
	ZHENG Y G，WANG Y J，XUE Y P，et al. Method for preparing acarbose through microbial fermentation: CN201010605821.X[P], 2011-08-03.
66	郑裕国，孙丽慧，李明刚，等. 微生物发酵合成阿卡波糖的方法: CN201110293699.1[P]. 2012-04-04.
	ZHENG Y G，SUN L H，LI M G，et al. Method for synthesizing acarbose through microbial fermentation: CN201110293699.1[P]. 2012-04-04.
67	ZARGAR A, BAILEY C B, HAUSHALTER R W, et al. Leveraging microbial biosynthetic pathways for the generation of ‘drop-in’ biofuels[J]. Current Opinion in Biotechnology, 2017, 45:156-163.
68	MA T, ZHOU Y, LI X, et al. Genome mining of astaxanthin biosynthetic genes from Sphingomonas sp. ATCC 55669 for heterologous overproduction in Escherichia coli[J]. Biotechnology Journal, 2016, 11(2): 228-237.
69	MA T, SHI B, YE Z, et al. Lipid engineering combined with systematic metabolic engineering of Saccharomyces cerevisiae for high-yield production of lycopene[J]. Metabolic Engineering, 2019, 52:134-142.
70	BIAN G, HAN Y, HOU A, et al. Releasing the potential power of terpene synthases by a robust precursor supply platform[J]. Metabolic Engineering, 2017, 42:1-8.

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