Accumulation of an organic anticancer selenium compound in a transgenic Solanaceous species shows wider applicability of the selenocysteine methyltransferase transgene from selenium hyperaccumulators

Abstract

Tolerance to high selenium (Se) soils in Se-hyperaccumulating plant species is correlated with the ability to biosynthesise methylselenocysteine (MeSeCys), due to the activity of selenocysteine methyltransferase (SMT). In mammals, inclusion of MeSeCys in the diet reduces the incidence of certain cancers, so increasing the range of crop plants that can produce this compound is an attractive biotechnology target. However, in the non-Se accumulator Arabidopsis, overexpression of SMT does not result in biosynthesis of MeSeCys from selenate because the rate at which selenate is reduced to selenite by ATP sulfurylase (ATPS) is low. This limitation is less problematic in other species of the Brassicaceae that can produce MeSeCys naturally. We investigated the potential for biosynthesis of MeSeCys in other plant families using Nicotiana tabacum L., a member of the Solanaceae. When plants were watered with 200 microM selenate, overexpression of a SMT transgene caused a 2- to 4-fold increase in Se accumulation (resulting in increased numbers of leaf lesions and areas of necrosis), production of MeSeCys (up to 20% of total Se) and generation of volatile dimethyl diselenide derived directly from MeSeCys. Despite the greatly increased accumulation of total Se, this did not result in increased Se toxicity effects on growth. Overexpression of ATPS did not increase Se accumulation from selenate. Accordingly, lines overexpressing both ATPS and SMT did not show a further increase in total Se accumulation or in leaf toxicity symptoms relative to overexpression of SMT alone, but directed a greater proportion of Se into MeSeCys. This work demonstrates that the production of the cancer-preventing compound MeSeCys in plants outside the Brassicaceae is possible. We conclude that while the SMT gene from Se hyperaccumulators can probably be utilised universally to increase the metabolism of Se into MeSeCys, the effects of enhancing ATPS activity will vary depending on the species involved.

Mechanisms of the Selenium Tolerance of theArabidopsis thalianaKnockout Mutant of Sulfate Transporter SULTR1;2

“…8,37) In the present study, the percentage of organic Se in the sultr1;2 was significantly larger than that of the wild type in the presence of 250 mM selenate (Fig. 2D), suggesting that enzymes related to S assimilation are strongly activated by Se stress in sultr1;2, resulting in Se tolerance.…”

“…1,7) In this case, Se is assimilated into selenomethionine (SeMet), and subsequently is converted into a volatile compound, dimethylselenide (DMSe), which is released into the atmosphere. 8) Volatilization of Se is also favorable to Se tolerance, because the toxicity of DMSe is 500 to 700-fold lower than that of selenate. 9) Arabidopsis thaliana can also convert inorganic Se (e.g., selenite and selenate) to organic Se via the sulfur assimilation pathway.…”

“…9) Arabidopsis thaliana can also convert inorganic Se (e.g., selenite and selenate) to organic Se via the sulfur assimilation pathway. 8) Indian mustard (Brassica juncea) is moderately tolerant of Se. 10) Overexpression of sulfur assimilationrelated enzymes, including ATP sulfurylase and selenocystein methyltransferase, improves Se tolerance and increases Se accumulation in Indian mustard.…”

Selenium Metabolism in Plants: Molecular Approaches

“…Se tolerance was similar in the single and double transgenics. On the other hand, McKenzie et al (2009) concluded that while the SMT gene from Se hyperaccumulators can probably be utilised universally to increase the metabolism of Se into MeSeCys, the effects of enhancing ATP sulfurylase activity could vary depending on the species involved.…”

“…Numerous studies have demonstrated the efficacy of methylselenocysteine (MeSeCys) in preventing mammary cancer in mammalian model systems, and importantly, MeSeCys has been shown to be twice as active as Se-methionine (the primary component of Se-yeast supplements) in preventing the development of mammary tumors (Ip & Ganther, 1992;Lu et al, 1996;Ip et al, 2000;Finley and Davis 2001;Medina et al, 2001;McKenzie et al, 2009). This non-protein seleno amino acid is produced in certain plants including members of the Astragalus, Allium and Brassica genera (Cai et al, 1995;Clark et al, 1996).…”