STEROL METHYLTRANSFERASE 1 Controls the Level of Cholesterol in Plants

Abstract

The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol. The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes-sterol methyltransferase 1 ( SMT1) , SMT2, and SMT3-homologous to yeast ERG6 , which is known to encode an S -adenosylmethioninedependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p. Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition.

Cloning and characterization of a squalene synthase gene from a petroleum plant, Euphorbia tirucalli L.

“…In the EtSS-overexpressed calli SS103 and SS104, the amount of stigmasterol increased, while those of cycloartenol and 24-methylenecycloartanol decreased (Table 1). This suggests that 24-methyl transferase (Diener et al 2000), C-4 demethylase, and CYP710 (Morikawa et al 2006) are upregulated in these two callus lines. This phenomenon might be reinforced by characters speciWc to the wild type E. tirucalli callus used as the transformation host.…”

Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms

“…In this model, the sterol C14-demethylation reaction is part of the core sterol biosynthesis pathway which operates in cholesterol synthesis generally [1], and the sterol C24-methylation reaction provides the critical slow step that can yield phyla-specific 24-alkyl sterol patterning unique to T. brucei . In addition, the 24-SMT activity can serve to control the ratio of 24-alkyl sterol to cholestenols synthesized in the cells, as shown through genetic modulation of the Arabidopsis sitosterol pathway engineered to produce cholesterol [43]. To complete ergosterol biosynthesis from ETO, a sterol C22-desaturase (Figure 8, reaction 13→14) and sterol C25(27)-reductase enzyme (the corresponding gene of this enzyme is not evident in GenBank ® ; Figure 8, reaction 12→13) are required; notably, neither the Δ 25(27) -reductase enzyme nor multiple product Tb SMT has been reported in the T. cruzi sterol biosynthesis pathway.…”

Bio-crude transcriptomics: Gene discovery and metabolic network reconstruction for the biosynthesis of the terpenome of the hydrocarbon oil-producing green alga, Botryococcus braunii race B (Showa)*

“…This paper described the cloning, heterologous expression and functional characterization of six enzymes showing similarity to sterol 24- C -methyltransferases (SMT, E.C. 2.1.1.41) that catalyse single methyl additions onto the linear prenyl side chains of sterols using SAM as the methyl donor [73,74]. Three of these putative SMTs that harboured variant sterol binding domains were found to conduct two successive methyl transfers onto linear triterpenoids.…”