Open access peer-reviewed chapter

Biosynthesis Pathways of Vitamin E and Its Derivatives in Plants

Written By

Makhlouf Chaalal and Siham Ydjedd

Submitted: 18 October 2020 Reviewed: 16 March 2021 Published: 13 May 2021

DOI: 10.5772/intechopen.97267

Chapter metrics overview

1,079 Chapter Downloads

View Full Metrics


Naturally occurring vitamin E, comprised of four forms each of tocopherols and tocotrienols, are synthesized solely by photosynthetic organisms and function primarily as antioxidants. The structural motifs of the vitamin E family and specifically the chroman moiety, are amenable to various modifications in order to improve their bioactivities towards numerous therapeutic targets. Tocopherols are lipophilic antioxidants and together with tocotrienols belong to the vitamin-E family. These lipid-soluble compounds are potent antioxidants that protect polyunsaturated fatty acids from lipid peroxidation. Biosynthetic pathways of plants producing a diverse array of natural products that are important for plant function, agriculture, and human nutrition. Edible plant-derived products, notably seed oils, are the main sources of vitamin E in the human diet. The biosynthesis of tocopherols takes place mainly in plastids of higher plants from precursors derived from two metabolic pathways: homogentisic acid, an intermediate of degradation of aromatic amino acids, and phytyldiphosphate, which arises from methylerythritol phosphate pathway. Tocopherols and tocotrienols play an important roles in the oxidative stability of vegetable oils and in the nutritional quality of crop plants for human and livestock diets. Here, we review major biosynthetic pathways, including common precursors and competitive pathways of the vitamin E and its derivatives in plants.


  • Vitamin E
  • Biosynthetic pathways
  • Tocopherols
  • Tocochromanol
  • Shikimate pathway
  • Methylerythritol pathway

1. Introduction

Under biotic and abiotic stresses conditions, including pathogens, temperature, drought, salt, and high light, the reactive oxygen species (ROS) resulting the oxidation of cellular components, as proteins, chlorophyll, and lipids [1]. To defend against oxidative stress, the plants have developed two general protective mechanisms, enzymatic and non-enzymatic detoxification, of which the latter involves vitamin E [2].

Plants are a major source of vitamins in the human diet. Due to their significance for human health and development, research has been initiated to understand the biosynthesis of vitamins in plants [3]. Vitamin E is thought to be involved in many essential processes in animals and plants. The function of vitamin E in plants is far from being clear. Likewise, in animal cells, the vitamin E acts as an antioxidant, thus it protects the plant from oxygen toxicity.

Four different forms of tocopherols and tocotrienols occur in nature and differ by the numbers and positions of methyl groups on the aromatic portion of the chromanol head group (Figure 1).

Figure 1.

The eight forms of naturally occurring vitamin E (or tocochromanols) [4].

Only plants and some cyanobacteria are able to synthesise vitamin E. α-Tocopherol is the predominant form of vitamin E green parts of higher plants, and is synthesized and localised mainly in plastids, whereas generally in non-photosynthetic tissues, γ-tocopherol is the major form [5].

The accumulation of vitamin E was varied in a number of plant species and in different plant parts. Generally, their content was ranged between 100 and 500 mg/kg fresh weight of normal plants with some exceptions. Oil-yielding plants present a higher vitamin E amount. Likewise, the seeds showed a highest total vitamin E content compared to other plant parts. Table 1 indicates the amount of α-tocopherol in different plant species. In seeds, the vitamins were localized in plastids; however, in some cases it was also observed in cytoplasmic lipid bodies [6]. Commonly, α-Tocopherol was the major form of vitamin E in leaves, while many plants seeds contain γ-Tocopherol. Heowever, β-tocophenrol and δ-Tocophenrol are uncommon in plants [1, 7]. Thus, this work complements highlighted the biosynthetic origins of vitamin E biosynthetic precursors in plants.

SourcesPlant organsUsable ProductsVitamin E contents (g/kg)
PeanutSeedEdible nut172
MaizeSeedEntire grain20
AsparagusShoot Youngshoot15
SpinachLeafRaw leaf20
SpinachLeafCooked leaf21
TomatoFruitRaw fruit9
TobaccoLeafYoung leaf57
TobaccoLeafOld leaf180

Table 1.

Vitamin E content in different cultivated plant species (reported by Has).


2. Biosynthesis of vitamins in plants

The biosynthesis of different vitamins in plants has been carried out generally by bacterial pathways, except in the case of vitamin C, which is synthesized exclusively by eukaryotes. The biosynthesis of some vitamins is limited to the compartment as carotenoids (pro-vitamin A), vitamins E and K and water-soluble riboflavin are produced in the plastids of plants [8, 9]. However, some enzymes of phylloquinone biosynthesis have been found in peroxisomes [10] and riboflavin is further converted to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in the cytosol, plastids or mitochondria [11]. Furthermore, the biosynthesis of the water soluble vitamins is split between different compartments, including the mitochondria [12] (Figure 2).

Figure 2.

Cross-points on the biosynthetic pathways of vitamins in plants [13].

The vitamins precursors were coming from carbohydrate metabolism, which regulates the pools of hexoses, pentoses and trioses in the plastids and the cytosol. The pentose and triose pool in the plastids provides: (a) erythrose-P and phosphoenolpyruvate for the synthesis of chorismate, the common intermediary in the biosynthesis of tocochromanols [14, 15]; (b) glyceraldehyde 3-P and pyruvate (from phosphoenolpyruvate), which are required for the synthesis of geranylgeranyl-PP, a key shared precursor of lipid-soluble vitamins [8, 14].


3. Vitamin E structures and biosynthesis

Plants synthesize eight different molecules with vitamin E antioxidant activity, including α-, β-, γ-, and δ-tocopherols and the corresponding four tocotrienols. These forms were different with respect the number and position of the methyl groups on their chromanol ring. The tocotrienols have an unsaturated tail containing three double bonds, while the four tocopherols have a phytyl tail.

Two main pathways of vitamin E biosynthesis are occurs at the inner envelope of plastids. The shikimate pathway gives rise to the chromanol ring from homogentisate (HGA). While, the methylerytrithol phosphate (MEP) pathway provides the prenyl tail from geranylgeranyl diphosphate (GGDP) for the synthesis of tocotrienol and phytyl diphosphate (phytyl-DP) for the synthesis of tocopherol (Figure 3). Furthermore, an additional pathway for phytyl-DP production from chlorophyll degradation, also known as the phytol recycling pathway (Figure 4). Seeds and leaves showed 80% and 65% reductions in total tocopherol content, respectively, compared to other plant parts. Chlorophyll synthase and geranylgeranyl diphosphate reductase (GGDR) are also involved in vitamin E biosynthesis [17]. The identity of the enzymes involved in chlorophyll dephytylation is less clear and the hydrolases such as CLD1 may allow phytol remobilization during fruit ripening and seed maturation [18, 19].

Figure 3.

Vitamin E Chemical Structure and Biosynthesis in Plants [16]. (A) Vitamin E chemical structure. A chromanol head and a prenyl tail constitute the chemical structure of tocopherols and tocotrienols. While tocopherols have a saturated tail, tocochromonals have three unsaturations (orange lines), at 3', 7', and 11'. (B) Biosynthesis of tocopherols and tocotrienols in plants. Tocopherols and tocotrienols are formed from the combination of the methylerythritol phosphate and shikimate pathways.

Figure 4.

Tocopherol Biosynthesis with Chlorophyll Degradation in Plants [16].


4. Tocopherols biosynthetic pathway

Tocopherols are found in higher plants, in algae, and in some nonphotosynthetic plants, such as yeasts and mushrooms [20]. Tocopherol biosynthesis was carried out via the condensation of homogentisate, derived from the shikimate pathway, and phytyl pyrophosphate (phytyl-PP), derived from the non-mevalonate pathway, through the action of the homogentisate prenyltransferase (HPT) (Figure 5). Subsequent ring cyclization and methylation reactions result in the formation of the four major tocopherol derivatives. The final methylation reaction resulting inα - and β-tocopherol, respectively, is expected to be catalysed by the same methyltransferase (γ-TMT) [21]. Theγ -TMT gene was isolated from the putative 10-gene tocopherol biosynthetic operon in Synechocystis sp.

Figure 5.

Vitamin E biosynthetic pathway [21]. The blue box highlights the four naturally occurring tocopherol derivatives in plants.

4.1 Shikimate pathway

The shikimate pathway has been found in plants and in some microorganisms serves as a biosynthetic way of aromatic amino acids (phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp)), and as precursors for many secondary metabolites, such as pigments, vitamins, etc. [22]. It consists of seven steps where the glycolytic intermediate phosphoenol pyruvate and the pentose phosphate pathway intermediate erythrose-4-phosphate are converted in chorismate (Figure 6). Numerous synthases, dehydratases and kinases are involved in this pathway, but their participation in tocopherols biosynthesis is not clear. The limitation step in the shikimate pathway are the reversible formation of 5-enolpyruvylshikimate 3-phosphate (EPSP) and inorganic phosphate from shikimate 3-phosphate and phosphoenolpyruvate. Likewise, the reaction is catalyzed by EPSP synthase (EC, which is the unique target for herbicide glyphosate (N-phosphonomethylglycine) [24]. Glyphosate interacts with the binding site of phosphoenolpyruvate and forms a stable ternary complex with the enzyme and shikimate 3-phosphate Likewise, Chorismate is the end product of the shikimate pathway and, at the same time, is a precursor for many primary and secondary metabolites, such as vitamin-K, folates, alkaloids, quinones, tocopherols and three aromatic amino acids (Phe, Tyr and Trp) [23]. p-Hydroxyphenylpyruvate (HPP) is the first intermediate in tocopherol biosynthesis. Different ways of HPP synthesis exist in photosynthetic organisms. In higher plants, it is formed from prephenate via arogenate and tyrosine. A portion of fixed carbon is incorporated into Tyr used for biosynthesis of HPP and homogentisate, a tocochromanol (tocopherols and tocotrienols) precursor [25].

Figure 6.

The shikimate pathway of homogentisate biosynthesis in photosynthetic organisms [23].

The formation of homogentisate from HPP occurs in the reaction catalyzed by HPPD. Homogentisate may either enter the prenylquinone biosynthesis pathway or be metabolized by homogentisate dioxygenase (EC to yield maleylacetoacetate, which further is catabolized to fumarate and acetyl-CoA [23].

4.2 Methyl erythritol phosphate (MEP) synthesis

The plastidic 2C-methyl-D-erythritol 4-phosphate (MEP) pathway produces isopentenyl diphosphate (IPP) that is used for the biosynthesis of isoprenes, monoterpenes (C10), diterpenes (C20), carotenoids, plastoquinones, and phytol conjugates such as chlorophylls and tocopherols.

The first step in the MEP pathway involves a transketolase-type condensation reaction of pyruvate and glyceraldehyde 3-phosphate to form 1-deoxy-D-xylulose-5-phosphate (DOXP) (Figure 7), which is also an intermediate in the biosynthesis of thiamin and pyridoxol [26, 27, 28]. The formed isopentenyl diphosphate is further isomerized to DMAPP. However, the IPP is suggested to be the final production of the MEP pathway in higher plants [26]. The chlorophyll-derived phytol may be a precursor for the biosynthesis of tocopherols, because, the accumulation of tocopherol negatively correlated with chlorophyll content in some plant species during leaf senescence [29].

Figure 7.

Methylerythritol pathway of phytyl diphosphate biosynthesis in the plastids of higher plants [23].


5. Tocochromanol biosynthetic pathway

According to the degree of methylation of the chromanol ring, four different forms of tocochromanol was obtained (Figure 8). Four forms of tocopherol, tocotrienol, and tocomonoenol have been identified in wild-type plant extracts, only the solanesyl-derived tocochromanol PC-8form is exists in the nature [30].

Figure 8.

Tocochromanol (tocopherol, tocotrienol, tocomonoenol, and methyl PC-8) biosynthetic pathways in plants [30].

It has been assumed for a long time that tocochromanol biosynthesis was the exclusive appanage of plants, algae, and some cyanobacteria that are all photosynthetic organisms. Tocochromanol biosynthesis is initiated by the condensation of the polar aromatic head HGA with various lipophilic polyprenyl pyrophosphates that determine the type of tocochromanol. The condensation reaction is catalyzed by three types of HGA prenyltransferases that possess each their substrate specificities. Tocopherol synthesis is initiated by HGA phytyltransferases (HPTs) that condense HGA and PPP. The condensation between HGA and polyprenyl pyrophosphates produces 2-methyl-6-phytyl-1,4-benzoquinol (MPBQ), 2-methyl-6-geranylgeranyl- 1,4-benzoquinol (MGGBQ), 2-methyl-6-solanesyl-1,4-benzoquinol (MSBQ), and 2-methyl-6-tetrahydrogeranylgeranyl-1,4-benzoquinol (MTHGGBQ) for tocopherols, tocotrienols, PC-8, and for tocomonoenols, respectively (Figure 8). Finally, tocochromanol biosynthesis consists of the methylation of γ- and δ-tocochromanols intoα - and β-tocochromanols, respectively [31, 32]. In Arabidopsis leaves and seeds, VTE4 converts γ anjdδ -tocopherols intoα - and β-tocopherol, respectively [32]. In addition, transgenic Arabidopsis lines overexpressing the barley HGGT gene notably produceα -tocotrienol [33].


6. Conclusion

Vitamin E biosynthesis mobilizes two distinct biosynthetic pathways, the shikimate pathway and the MEP pathway. Indeed, the shikimate pathway gives rise to the chromanol ring from homogentisate (HGA). While, the methylerytrithol phosphate (MEP) pathway provides the prenyl tail from geranylgeranyl diphosphate (GGDP) and phytyl diphosphate (phytyl-DP) for the synthesis of tocotrienol and tocopherol, respectively. An additional pathway for phytyl-DP production from chlorophyll degradation, known as the phytol recycling pathway. Understanding the regulation of vitamin E biosynthesis will imply that we take up the challenges to understand the regulation of each of these numerous events. The fundamental role of this vitamin in human reproduction and its benefit in current widespread diseases such as high cholesterol and neurodegenerative pathologies makes it a candidate of choice to improve human health.

Acronyms and abbreviations


5-aminoimidazole ribonucleotide


chlorophyll dephytylase 1






dimethylallyl pyro-phosphate


geranylgeranyl diphosphate


geranylgeranyl diphosphate reductase


geranylgeranyl pyrophosphate


geranylgeranyl diphosphate synthase


4-methyl-5-b-hydroxyethyl thiazole phosphate


homogentisate geranylgeranyl transferase


2-methyl-4-amino-5-hydroxymethylpyrimidine diphosphate




hydroxyphenylpyruvate dioxygenase


homogentisate phytyl transferase


inosine monophosphate


isopentenyl pyrophosphate


methylerythritol phosphate






MPBQ methyltransferase


2-methyl-6-phytylhydroquinone methyltransferase


phytyl diphosphate


phytyl pyrophosphate






tyrosine aminotransferase


tocopherol cyclase


tocopherol methyltransferase.


  1. 1. Abbasi A-R, Hajirezaei M, Hofius D, Sonnewald U, Voll LM. Specific roles of α-and γ-tocopherol in abiotic stress responses of transgenic tobacco. Plant Physiology 2007;143:1720-1738
  2. 2. Alscher RG, Erturk N, Heath LS. Role of superoxide dismutases (SODs) in controlling oxidative stress in plants. Journal of Experimental Botany 2002;53:1331-1341
  3. 3. Herbers K. Vitamin production in transgenic plants. Journal of Plant Physiology 2003;160:821
  4. 4. Hunter SC, Cahoon EB. Enhancing Vitamin E in Oilseeds: Unraveling Tocopherol and Tocotrienol Biosynthesis. Lipids 2007; 42:97-108
  5. 5. Munné-Bosch S, Alegre L. The function of tocopherols and tocotrienols in plants. Critical Reviews in Plant Sciences 2002;21:31-s57
  6. 6. White DA, Fisk ID, Gray DA. Characterisation of oat (Avena sativa L.) oil bodies and intrinsically associated E-vitamers. Journal of Cereal Science 2006;43:244-249
  7. 7. Hussain N, Irshad F, Jabeen Z, Shamsi IH, Li Z, Jiang L. Biosynthesis, structural, and functional attributes of tocopherols in planta; past, present, and future perspectives. Journal of Agricultural and Food Chemistry 2013;61:6137-6149
  8. 8. Rodríguez-Villalón A, Gas E, Rodríguez-Concepción M. Phytoene synthase activity controls the biosynthesis of carotenoids and the supply of their metabolic precursors in dark-grown Arabidopsis seedlings. The Plant Journal 2009;60:424-435
  9. 9. Sandoval FJ, Zhang Y, Roje S. Flavin nucleotide metabolism in plants monofunctional enzymes synthesize FAD in plastids. Journal of Biological Chemistry 2008;283:30890-30900
  10. 10. Babujee L, Wurtz V, Ma C, Lueder F, Soni P, Van Dorsselaer A, et al. The proteome map of spinach leaf peroxisomes indicates partial compartmentalization of phylloquinone (vitamin K1) biosynthesis in plant peroxisomes. Journal of Experimental Botany 2010;61:1441-1453
  11. 11. Sinclair SJ, Murphy KJ, Birch CD, Hamill JD. Molecular characterization of quinolinate phosphoribosyltransferase (QPRTase) in Nicotiana. Plant Molecular Biology 2000;44:603-617
  12. 12. Roje S. Vitamin B biosynthesis in plants. Phytochemistry 2007;68:1904-1921
  13. 13. Asensi-Fabado MA, Munné-Bosch S. Vitamins in plants: occurrence, biosynthesis and antioxidant function. Trends Plant Science 2010; 15:582-92
  14. 14. DellaPenna D, Last RL. Progress in the dissection and manipulation of plant vitamin E biosynthesis. Physiologia Plantarum 2006;126:356-368
  15. 15. Sahr T, Ravanel S, Basset G, Nichols BP, Hanson AD, Rébeillé F. Folate synthesis in plants: purification, kinetic properties, and inhibition of aminodeoxychorismate synthase. Biochemical Journal 2006;396:157-162
  16. 16. Muñoz P, Munné-Bosch S. Vitamin E in Plants: Biosynthesis, Transport, and Function. Trends Plant Science 2019; 24:1040-1051
  17. 17. Zhang C, Zhang W, Ren G, Li D, Cahoon RE, Chen M, et al. Chlorophyll synthase under epigenetic surveillance is critical for vitamin E synthesis, and altered expression affects tocopherol levels in Arabidopsis. Plant Physiology 2015;168:1503-1511
  18. 18. Lin Y-P, Wu M-C, Charng Y. Identification of a chlorophyll dephytylase involved in chlorophyll turnover in Arabidopsis. The Plant Cell 2016;28:2974-2990
  19. 19. Zhang X, Song J, Shi X, Miao S, Li Y, Wen A. Absorption and metabolism characteristics of rutin in Caco-2 cells. The Scientific World Journal 2013;2013
  20. 20. Threlfall DR. The biosynthesis of vitamins E and K and related compounds. Vitamins & Hormones, vol. 29, Elsevier; 1971, p. 153-200
  21. 21. Hofius D, Sonnewald U. Vitamin E biosynthesis: biochemistry meets cell biology. Trends in Plant Science 2003;8:6-8
  22. 22. Herrmann KM, Weaver LM. The shikimate pathway. Annual Review of Plant Biology 1999;50:473-503
  23. 23. Lushchak VI, Semchuk NM. Tocopherol biosynthesis: chemistry, regulation and effects of environmental factors. Acta Physiologiae Plantarum 2012;34:1607-1628
  24. 24. Herrmann KM. The shikimate pathway: early steps in the biosynthesis of aromatic compounds. The Plant Cell 1995;7:907
  25. 25. Rippert P, Scimemi C, Dubald M, Matringe M. Engineering plant shikimate pathway for production of tocotrienol and improving herbicide resistance. Plant Physiology 2004;134:92-100
  26. 26. Lichtenthaler HK. Non-mevalonate isoprenoid biosynthesis: enzymes, genes and inhibitors. Portland Press Ltd.; 2000
  27. 27. Rohmer M. Mevalonate-independent methylerythritol phosphate pathway for isoprenoid biosynthesis. Elucidation and distribution. Pure and Applied Chemistry 2003;75:375-388
  28. 28. Wanke M, Skorupinska-Tudek K, Swiezewska E. Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway. Acta Biochimica Polonica 2001;48:663-672
  29. 29. Valentin HE, Lincoln K, Moshiri F, Jensen PK, Qi Q , Venkatesh TV, et al. The Arabidopsis vitamin E pathway gene5-1 mutant reveals a critical role for phytol kinase in seed tocopherol biosynthesis. The Plant Cell 2006;18:212-224
  30. 30. Mène-Saffrané L. Vitamin E biosynthesis and its regulation in plants. Antioxidants 2018;7:2
  31. 31. Bergmüller E, Porfirova S, Dörmann P. Characterization of an Arabidopsis mutant deficient in γ-tocopherol methyltransferase. Plant Molecular Biology 2003;52:1181-1190
  32. 32. Shintani D, DellaPenna D. Elevating the vitamin E content of plants through metabolic engineering. Science 1998;282:2098-2100
  33. 33. Cahoon EB, Hall SE, Ripp KG, Ganzke TS, Hitz WD, Coughlan SJ. Metabolic redesign of vitamin E biosynthesis in plants for tocotrienol production and increased antioxidant content. Nature Biotechnology 2003;21:1082-1087

Written By

Makhlouf Chaalal and Siham Ydjedd

Submitted: 18 October 2020 Reviewed: 16 March 2021 Published: 13 May 2021