If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Synonyms: oleanolate glucuronide triterpene saponin biosynthesis, oleanolate glucuronide biosynthesis, triterpene saponin biosynthesis II
|Superclasses:||Biosynthesis → Secondary Metabolites Biosynthesis → Terpenoids Biosynthesis → Triterpenoids Biosynthesis|
Some taxa known to possess this pathway include : Calendula officinalis
Expected Taxonomic Range: Embryophyta
Oleanolate, a common triterpene derived from β-amyrin, can be found in its free form in plants, but is also subject to glycosylation. Oleanolate and its derivatives have been detected in at least 120 species of plants and exhibit numerous biological activities that can contribute to plant defense and human health. Anti-ulcer [Farina98], anti-nociceptive [Inoue90], anti-tumor [Miles74], anti-viral [Dargan85] and other beneficial activities have all been attributed to oleanolic triterpene saponins.
During oleanolate glycosylation, sugar moieties are typically attached to the C-3 hydroxyl group or the C-28 on the carboxyl group of oleanolate [Szakiel05]. Oleanolate derivatives can be separated into two major classes, glucosides and glucuronides, based on the nature of the initial glycosylation they undergo. The first step in oleanolate glucoside synthesis occurs when glucose is added to the C-3 hydroxyl group. Subsequent addition of glucose and/or galactose residues at the C-3 or C-28 positions leads to the formation of at least seven additional glucosides in Calendula officinalis (marigold), but the biochemical steps involved have not been well characterized. Meanwhile, oleanolate glucuronides arise from the addition of a glucuronic acid to the C-3 hydroxyl group, catalyzed by oleanolate UDP glucuronosyltransferase. Further glucosylations on oleanolate 3-beta-D-glucuronoside generate at least five additional glucuronides in marigold [Wojciechowski75, Szakiel05].
Oleanolate glucuronides share some properties that distinguish them from their glucoside counterparts. For example, in feeding experiments, the rate of glucoside biosynthesis exceeds the rate of glucuronide biosynthesis [Szyja83] and the rates of glucuronide and glucoside biosynthesis are differentially affected by light, and the hormones auxin and cytokinin [Szakiel03]. In addition, oleanolate glucuronides can be passively and irreversibly transported into vacuoles, whereas oleanolate glucoside transport into vacuoles is active and reversible [Szakiel02]. Thus, oleanolate glucuronides appear to behave more like traditional secondary metabolites in this respect. And, although each compound may have unique biological activities, in general, glucuronides tend to have lower allelopathic, but higher antifungal and wormicidal activity than the oleanolate glucosides. These classes of compounds also have different patterns of distribution within the plants that may be linked to their different biological functions [Szakiel05].
Despite the prevalence of these compounds in the plant kingdom, much remains to be discovered about their biosynthesis. Currently, little is known about the reactions that occur to transform β-amyrin into oleanolate, but a hypothetical reduction series of beta-amyrin to erythrodiol to oleanolic aldehyde to oleanolate was proposed in Machaerium incorruptible [Alves66]. Downstream of oleanolate, the synthesis of glycosylated derivatives has been studied in the medicinal and ornamental plant marigold [Wojciechowski75, Szakiel05]. Immediately downstream of oleanolate, the enzyme responsible for the first committed step in oleanolate glucuronide biosynthesis, oleanolate UDP glucuronosyltransferase, has been partially purified and characterized in the microsomal fraction of marigold seedling extracts [Wojciechowski75]. The downstream enzymes that add additional galactose and glucose residues have not been well-characterized, but a series of feeding experiments have led to a proposed biosynthetic pathway for these oleanolate saponins. There is some evidence that the biosynthesis of these compounds occurs in several parts of the cell. For instance, the enzyme(s) responsible for the addition of UDP-glucose to the C28 carboxyl residue in oleanolate and its derivatives appear to reside in the cytoplasm based on subcellular fractionation results [Wojciechowski75]. Meanwhile, the addition of galactose and/or glucose residues to the glucuronic acid may be performed in the Golgi complex [Wojciechowski75]. Though the enzyme(s) responsible for these glycosylations have not been isolated, the reactions do appear to proceed in a somewhat fixed order; feeding experiments suggest that the glucose cannot be attached to the glucuronic acid prior to galactose addition [Wojciechowski75].
Oleanolate glucuronide synthesis can occur in the leaf, roots, and in suspension cultures, though some later glycosylation reactions are organ-specific [Szakiel05], and this process appears to go on throughout the life cycle of the plant [Szakiel02].
Dargan85: Dargan DJ, Subak-Sharpe JH (1985). "The effect of triterpenoid compounds on uninfected and herpes simplex virus-infected cells in culture. I. Effect on cell growth, virus particles and virus replication." J Gen Virol 66 ( Pt 8);1771-84. PMID: 2991440
Inoue90: Inoue H, Kurosu S, Takeuchi T, Mori T, Shibata S (1990). "Glycyrrhetinic acid derivatives: anti-nociceptive activity of deoxoglycyrrhetol dihemiphthalate and the related compounds." J Pharm Pharmacol 42(3);199-200. PMID: 1974618
Miles74: Miles DH, Kokpol U, Zalkow LH, Steindel SJ, Nabors JB (1974). "Tumor inhibitors. I. Preliminary investigation of antitumor activity of Sarracenia flava." J Pharm Sci 63(4);613-5. PMID: 4828716
Szakiel02: Szakiel, Anna, Janiszowska, Wirginia (2002). "The mechanism of oleanolic acid monoglycosides transport into vacuoles isolated from Calendula officinalis leaf protoplasts." Plant Physiology and Biochemistry. 40(3):203-209.
Szakiel03: Szakiel, Anna, Grzelak, Anna, Dudek, Paulina, Janiszowska, Wirginia (2003). "Biosynthesis of oleanolic acid and its glycosides in Calendula officinalis suspension culture." Plant Physiology and Biochemistry. 41(3): 271-275.
Szakiel05: Szakiel, Anna, Ruszkowski, Dariusz, Janiszowska, Wirginia (2005). "Saponins in Calendula officinalis L. - structure, biosynthesis, transport and biological activity." Phytochemistry Reviews. 4:151-158.
Szyja83: Szyja, Wieswa, Wilkomirski, Boguslaw, Kasprzyk, Zofia (1983). "Biosynthesis of oleanolic acid glycosides in isolated ligulate flowers of calendula officinalis." Phytochemistry. 22(1):111-113.
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