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MetaCyc Pathway: isopimaric acid biosynthesis

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Terpenoids Biosynthesis Diterpenoids Biosynthesis Resin Acids Biosynthesis

Some taxa known to possess this pathway include ? : Abies grandis , Picea abies , Pinus taeda

Expected Taxonomic Range: Pinidae

Summary:
General Background

Oleoresin (also simply termed 'resin' or 'pitch') is a viscous secretion common in coniferous trees, which is involved in the chemical and physical defense of conifers against predators (such as bettles and fungal pathogens). The accumulated resin is released upon tissue injury and/or produced at the site of infestation (for review, see [Trapp01]). The predator is killed, encased in resin and expelled from the bore point of entry (a process called 'pitching out'). This process has the dual function of killing and expelling the predator, but also to form a physical barrier around the wound through evaporation of the oleoresin turpentine which allows the resin acids to seal the wound [Croteau85, Gijzen93]. Oleoresin is composed in roughly equal parts of volatile turpentine (a mixture of monoterpenes and sesquiterpenes) and rosin (also known as diterpene resin acids). The exact composition of turpentine and rosin varies from one conifer species to the next, as well as depending on the resin-producing tissue analyzed [Trapp01]. The main constituents of these fractions have been regrouped in the following pathways: superpathway of oleoresin turpentine biosynthesis and superpathway of diterpene resin acids biosynthesis.

Concerning this pathway:

Diterpene resin acids (DRAs) are major constituents of conifer oleoresin. They play important roles in conifer defense against insects (e.g. bark boring beetle) and microbial pathogens. DRAs are usually classified into two main categories: abietanes and pimaranes. Abietane-type diterpenes have been known to possess a variety of biological activities, such as antibacterial [Kobayashi88], cardiovascular [Ulubelen00], antioxidant [Lee06] and aldose reductase and α-glucosidase inhibitory activities [Matsuda99]. DRAs of the abietane family, characterized by the perhydrophenanthrene-type tricyclic ring structure of normal absolute configuration (C10 β-methyl) with an isopropyl group at C13 of the C ring, are the principal constituents of the rosin fraction of grand fir (Abies grandis) oleoresin [Peters00]. Pimarene-type diterpenes have been involved in a variety of biological processes: inhibition of platelet formation [Cheung94], antimicrobial activity [Ulubelen97, Smith05], or anti-inflammatory agents [Ulubelen97] (for review, see [Cheung94]).

Isopimaric acid, an pimarane-type DRA, is one of the principal resin acids [Kersten06, Tomlin00]. This compound has been shown to have antimicrobial properties when used against multidrug-resistant and EMRSA strains of Staphylococcus aureus [Smith05]. Moreover, isopimaric acid was demonstrated to inhibit strongly spore germination of the ascomycete Ophiostoma ips (a parasitic fungus closely associated with bark-boring beetle) [Kopper05]. The formation of this acid involves the formation of the pimarane skeleton via cyclization of the diterpenoid precursor geranylgeranyl diphosphate. This cyclization occurs via the formation of the intermediate (+)-copalyl diphosphate and is followed by the stepwise oxidation of the C18 methyl group of the derived olefin (+)-isopimara-7,15-diene. Several abietadiene synthases have been identified, which can produce a variety of other olefins including (+)-isopimara-7,15-diene [Vogel96, Martin04, Ro06]. The mechanism of oxidation of (+)-isopimara-7,15-diene to isopimaric acid resembles that of the oxidation of ent-kaurene to ent-kaur-16-en-19-oate and that ent-kaur-16-en-19-oate to gibberellin A12 (see GA12 biosynthesis) in which a single multifunctional enzyme (ent-kaurene oxidase) catalyze the consecutive oxidation steps. No single enzyme has been found to date that could catalyze all three conversion steps from (+)-isopimara-7,15-diene to isopimaric acid, however, one enzyme from Pinus taeda (loblolly pine) could catalyze the two oxidation steps between isopimaradienol and isopimaric acid [Ro05]. This same enzyme was additionally shown to be involved in the formation of other diterpene resin acids (such as dehydroabietate, levopimaric acid and neoabietic acid) [Ro05]. To date, however, no enzyme catalyzing the first step of oxidation of (+)-isopimara-7,15-diene to isopimaradienol has been identified.

Citations: [LaFever94]

Superpathways: superpathway of diterpene resin acids biosynthesis

Credits:
Created 05-Dec-2006 by Tissier C , TAIR


References

Cheung94: Cheung HT, Fu SL, Smal MA (1994). "Inhibition of platelet aggregation by diterpene acids from Pinus massoniana resin." Arzneimittelforschung 44(1);17-25. PMID: 8135873

Croteau85: Croteau R., Johnson M.A. (1985). "Biosynthesis of terpenoid wood extractives." In Biosynthesis and biodegradation of wood components, ed. T. Higuichi, pp 379-439.

Gijzen93: Gijzen M., Lewinsohn E., Croteau R. (1993). "Conifer monoterpenes: biochemistry and bark beetle chemical ecology." In Bioactive volatile compounds from plants, eds R. Teranishi, R.G. Buttery, H. Sugisawa, pp. 8-22, Washington DC: Am. Chem. Soc.

Kersten06: Kersten PJ, Kopper BJ, Raffa KF, Illman BL (2006). "Rapid analysis of abietanes in conifers." J Chem Ecol 32(12);2679-85. PMID: 17082986

Kobayashi88: Kobayashi, K., Masako, N., Fukushima, M., Shiobara, Y., Kodama, M. (1988). "Antibacterial activity oif pisiferic acid and its derivatives against Gram-negative and -positive bacteria.Agric. ." Agric. Biol. Chem. 52:77-83.

Kopper05: Kopper, B.J., Illman, B.L., Kersten, P.J., Klepsig, K.D., Raffa, K.F. (2005). "Effects of diterpene acids on components of a conifer Bark Beetle–Fungal interaction: tolerance by Ips pini and sensitivity by its associate Ophiostoma ips." Environ. Entomol. 34(2):486-493.

LaFever94: LaFever RE, Vogel BS, Croteau R (1994). "Diterpenoid resin acid biosynthesis in conifers: enzymatic cyclization of geranylgeranyl pyrophosphate to abietadiene, the precursor of abietic acid." Arch Biochem Biophys 313(1);139-49. PMID: 8053674

Lee06: Lee WS, Kim JR, Han JM, Jang KC, Sok DE, Jeong TS (2006). "Antioxidant activities of abietane diterpenoids isolated from Torreya nucifera leaves." J Agric Food Chem 54(15);5369-74. PMID: 16848519

Martin04: Martin DM, Faldt J, Bohlmann J (2004). "Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily." Plant Physiol 135(4);1908-27. PMID: 15310829

Matsuda99: Matsuda H, Murakami T, Yashiro K, Yamahara J, Yoshikawa M (1999). "Antidiabetic principles of natural medicines. IV. Aldose reductase and qlpha-glucosidase inhibitors from the roots of Salacia oblonga Wall. (Celastraceae): structure of a new friedelane-type triterpene, kotalagenin 16-acetate." Chem Pharm Bull (Tokyo) 47(12);1725-9. PMID: 10748716

Peters00: Peters RJ, Flory JE, Jetter R, Ravn MM, Lee HJ, Coates RM, Croteau RB (2000). "Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme." Biochemistry 39(50);15592-602. PMID: 11112547

Ro05: Ro DK, Arimura G, Lau SY, Piers E, Bohlmann J (2005). "Loblolly pine abietadienol/abietadienal oxidase PtAO (CYP720B1) is a multifunctional, multisubstrate cytochrome P450 monooxygenase." Proc Natl Acad Sci U S A 102(22);8060-5. PMID: 15911762

Ro06: Ro DK, Bohlmann J (2006). "Diterpene resin acid biosynthesis in loblolly pine (Pinus taeda): functional characterization of abietadiene/levopimaradiene synthase (PtTPS-LAS) cDNA and subcellular targeting of PtTPS-LAS and abietadienol/abietadienal oxidase (PtAO, CYP720B1)." Phytochemistry 67(15);1572-8. PMID: 16497345

Smith05: Smith E, Williamson E, Zloh M, Gibbons S (2005). "Isopimaric acid from Pinus nigra shows activity against multidrug-resistant and EMRSA strains of Staphylococcus aureus." Phytother Res 19(6);538-42. PMID: 16114093

Tomlin00: Tomlin ES, Antonejevic E, Alfaro RI, Borden JH (2000). "Changes in volatile terpene and diterpene resin acid composition of resistant and susceptible white spruce leaders exposed to simulated white pine weevil damage." Tree Physiol 20(16);1087-95. PMID: 11269960

Trapp01: Trapp S, Croteau R (2001). "Defensive resin biosynthesis in conifers." Annu Rev Plant Physiol Plant Mol Biol 52;689-724. PMID: 11337413

Ulubelen00: Ulubelen A, Oksuz S, Kolak U, Birman H, Voelter W (2000). "Cardioactive terpenoids and a new rearranged diterpene from Salvia syriaca." Planta Med 66(7);627-9. PMID: 11105567

Ulubelen97: Ulubelen A, Topcu G, Johansson CB (1997). "Norditerpenoids and diterpenoids from Salvia multicaulis with antituberculous activity." J Nat Prod 60(12);1275-80. PMID: 9428161

Vogel96: Vogel BS, Wildung MR, Vogel G, Croteau R (1996). "Abietadiene synthase from grand fir (Abies grandis). cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase involved in resin acid biosynthesis." J Biol Chem 271(38);23262-8. PMID: 8798524

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mafu11: Mafu S, Hillwig ML, Peters RJ (2011). "A novel labda-7,13e-dien-15-ol-producing bifunctional diterpene synthase from Selaginella moellendorffii." Chembiochem 12(13);1984-7. PMID: 21751328

Sugai11: Sugai Y, Ueno Y, Hayashi K, Oogami S, Toyomasu T, Matsumoto S, Natsume M, Nozaki H, Kawaide H (2011). "Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii." J Biol Chem 286(50);42840-7. PMID: 22027823


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Nov 22, 2014, BIOCYC13A.