Metabolic Origins and Transport of Vitamin E Biosynthetic Precursors

Abstract

Tocochromanols are organic compounds mostly produced by photosynthetic organisms that exhibit vitamin E activity in animals. They result from the condensation of homogentisate with four different polyprenyl side chains derived all from geranylgeranyl pyrophosphate. The core tocochromanol biosynthesis has been investigated in several photosynthetic organisms and is now well-characterized. In contrast, our current knowledge of the biosynthesis and transport of tocochromanol biosynthetic precursors is much more limited. While tocochromanol synthesis occurs in plastids, converging genetic data in Arabidopsis and soybean demonstrate that the synthesis of the polar precursor homogentisate is located in the cytoplasm. These data implies that tocochromanol synthesis involves several plastidic membrane transporter(s) that remain to be identified. In addition, the metabolic origin of the lipophilic isoprenoid precursor is not fully elucidated. While some genetic data exclusively attribute the synthesis of the prenyl component of tocochromanols to the plastidic methyl erythritol phosphate pathway, multiple lines of evidence provided by feeding experiments and metabolic engineering studies indicate that it might partially originate from the cytoplasmic mevalonate pathway. Although this question is still open, these data demonstrate the existence of membrane transporter(s) capable of importing cytosolic polyprenyl pyrophosphate such as farnesyl pyrophosphate into plastids. Since the availability of both homogentisate and polyprenyl pyrophosphates are currently accepted as major mechanisms controlling the type and amount of tocochromanols produced in plant tissues, we summarized our current knowledge and research gaps concerning the biosynthesis, metabolic origins and transport of tocochromanol biosynthetic precursors in plant cells.

Vitamin E Biosynthesis and Its Regulation in Plants

“…The present review summarizes our current knowledge on tocochromanol metabolism in plants, including the core tocochromanol biosynthetic pathway that is now well delineated ( Section 2 ); the transcriptional regulation of γ- TMT expression, which is the gene encoding the biosynthetic enzyme of the most potent vitamin E form of α-tocopherol in animals ( Section 3 ); the regulation of homogentisate (HGA) biosynthesis, which is the polar precursor of tocochromanols ( Section 4 ); and the regulation of polyprenyl pyrophosphate biosynthesis, which is the lipophilic precursor of tocochromanols ( Section 5 ). Thus, this work complements the very recent review that highlighted the biosynthetic origins and transports of polar and lipophilic tocochromanol biosynthetic precursors in plants [ 17 ].…”

“…Tocochromanol biosynthesis is initiated by the condensation of the polar aromatic head HGA with various lipophilic polyprenyl pyrophosphates that determine the type of tocochromanol. PPP is the lipophilic biosynthetic precursor of tocopherols, while GGPP is the one for tocotrienols, as is SPP for PC-8, and THGGPP for tocomonoenols (Pellaud and Mène-Saffrané, 2017 [ 17 ] and Figure 1 ). The condensation reaction is catalyzed by three types of HGA prenyltransferases that possess each their substrate specificities.…”

“…A corpus of biochemical, genetic, and cell biology data indicate that the cellular compartment hosting HGA biosynthesis is different among plant species. This aspect of tocochromanol biosynthesis has been recently reviewed in detail [ 17 ]. In the genetic model Arabidopsis, several studies have provided evidence that HGA biosynthesis is confined to the cytoplasm.…”

Strategies for the production of biochemicals in bioenergy crops

“…2, 4a). Phytyl diphosphate (phytyl-PP) generated by geranylgeranyl reductase (GGR) [236,237] is condensed with HGA by HGA phytyltransferase (HPT) to generate tocopherol precursors, while tocotrienol precursors result from the coupling of GGPP to HGA mediated by HGA geranylgeranyltransferase (HGGT) [230,238]. These precursors undergo cyclization by tocopherol cyclase (TC) and methylation by methyltransferase (MT) to produce the δ-and γ-form, respectively.…”

“…Additional methylations catalyzed by γ-TMT generate the α-and β-forms of tocopherols. In Arabidopsis, VTE2, VTE3, VTE1 and VTE4 are the enzymes corresponding to HPT, MT, TC, and γ-TMT [238]. Exogenous expression of HvHGGT from barley in Arabidopsis resulted in 10-to 15-fold increase in total vitamin E antioxidants (i.e., tocotrienols plus tocopherols), while in corn seeds, sixfold increase was achieved using the same strategy [239].…”