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MetaCyc Pathway: matairesinol biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Phenylpropanoid Derivatives Biosynthesis Lignans Biosynthesis

Some taxa known to possess this pathway include ? : Forsythia x intermedia , Podophyllum peltatum , Thuja plicata

Expected Taxonomic Range: Viridiplantae

Summary:
General Background

Lignans are a group of dimeric and/or oligomeric plant natural compounds of phenylpropanoid origin. They represent a structurally highly diverse compound class that is characterized by a 8,8'-linkage found in the C6-C3 dimers of coniferyl alcohol or other cinnamoyl alcohols although other interunit linkages (e.g. 8-5', 8-O-4) may also occur [Lewis99] [Fuss03].

Lignans and lignins are biosynthesized in two major branches which descend from the phenylpropanoid pathway. During the conquest of land this pathway has been substantially advanced with consequences for derivative biosyntheses such as for lignins/lignans, hydrolyzable and condensed tannins and flavonoids [Stafford00]. Lignans are widespread among the plant kingdom but have not been found in aquatic plants such as algae indicating their crucial contribution to adaptation and fitness of terrestrial plants [Ayres90] [Burlat01]. The structural biopolymers lignins and lignans accomplish different tasks in plants, lignins are involved in structural support and lignans have been attributed to protection and defense as their primary physiological functions. Taken together lignins and lignans count for about 30% of carbon in vascular plants [Lewis99].

Beside their recognized functions as defense compounds in plants some lignans have attracted the attention of scientists because of their application in medicine and human health [MacRae84]. Lignans possess most effective health protective and curative properties and have been employed as antioxidants [Bloedon04], anti-carcinogenic agents [Ford99] [Saleem05] and phytoestrogens [Dixon04].

Lignans can be subdivided into several structural subfamilies. The matairesinol pathway is an excellent example for a pathway that not only contains several types of lignans but also gives rise to other lignan subfamilies. (+)-pinoresinol (a furofuran) is sequentially converted to (+)-lariciresinol (a benzylaryltetrahydrofuran), (-)-secoisolariciresinol (a dibenzylbutane) and (-)-matairesinol (a dibenzylbutyrolactone) which is an intermediate in the biosynthetic route towards podophyllotoxin (an aryltetrahydronaphthalene) (compare podophyllotoxin and 6-methoxypodophyllotoxin biosynthesis).

About This Pathway

Most lignans are optically active which results from the stereo-specific linkage that builds the various dimers. The unique protein that mediates the regio- and stereospecificity of bimolecular phenoxy radical coupling to generate oligomeric lignans and polymeric lignins has been identified and characterized [Davin97]. It could be demonstrated that this protein forms a multigene family in plants [Kim02c] which are not limited to the formation of lignans but has been found to be involved in other biosyntheses of various phenolics employing corresponding radicals. The protein named 'dirigent protein' (DP) does not express any catalytic activity and serves only to bind and orientate the coniferyl alcohol-derived free radicals [Davin00] [Davin05]. The first step of the biosynthesis therefore includes two proteins, one enzyme which may be a unspecific oxidase and/or laccase and the dirigent protein mediating the radical-radical coupling with two coniferyl alcohol radical substrates [Halls02] [Halls04].

Two distinct enzyme classes of (+)-pinoresinol/(+)-lariciresinol reductase (PLR) have been identified that catalyze the second step in the matairesinol biosynthesis. Those enzymes are bifunctional and catalyze the enantioselective reduction of (+)-pinoresinol and (+)-lariciresinol towards (-)-secoisolaricinol as discovered in Forsythia [DinkovaKostova96] - left branch of the pathway- or engenders the formation of the opposite enantiomer (+)-secoisolariciresinol from (-)-pinoresinol and (-)-lariciresinol intermediates as demonstrated in western red cedar [Fujita99] - right branch of the pathway. Those enantiospecific enzymes have also been found in different species of the same genus [vonHeimendahl05].

Another bifunctional enzyme, i.e. (-)-secoisolariciresinol dehydrogenase (SDH) affords the formation of (-)-matairesinol [Umezawa91] via the stable intermediate (-)-lactol [Xia01]. The reaction mechanism was investigated in detail by means of the crystallized protein and it was shown that a catalytic triad with a strictly conserved tyrosine residue [Youn05] was essential for catalytic activity [Moinuddin06].

Credits:
Created 31-Jan-2007 by Foerster H , TAIR


References

Ayres90: Ayres DC, Loike JD (1990). "Chemistry and pharmacology of natural products. Lignans: Chemical, biological and clinical properties." Cambridge University Press, Cambridge.

Bloedon04: Bloedon LT, Szapary PO (2004). "Flaxseed and cardiovascular risk." Nutr Rev 62(1);18-27. PMID: 14995053

Burlat01: Burlat V, Kwon M, Davin LB, Lewis NG (2001). "Dirigent proteins and dirigent sites in lignifying tissues." Phytochemistry 57(6);883-97. PMID: 11423139

Davin00: Davin LB, Lewis NG (2000). "Dirigent proteins and dirigent sites explain the mystery of specificity of radical precursor coupling in lignan and lignin biosynthesis." Plant Physiol 123(2);453-62. PMID: 10859176

Davin05: Davin LB, Lewis NG (2005). "Dirigent phenoxy radical coupling: advances and challenges." Curr Opin Biotechnol 16(4);398-406. PMID: 16023845

Davin97: Davin LB, Wang HB, Crowell AL, Bedgar DL, Martin DM, Sarkanen S, Lewis NG (1997). "Stereoselective bimolecular phenoxy radical coupling by an auxiliary (dirigent) protein without an active center." Science 275(5298);362-6. PMID: 8994027

DinkovaKostova96: Dinkova-Kostova AT, Gang DR, Davin LB, Bedgar DL, Chu A, Lewis NG (1996). "(+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia. Protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase." J Biol Chem 271(46);29473-82. PMID: 8910615

Dixon04: Dixon RA (2004). "Phytoestrogens." Annu Rev Plant Biol 55;225-61. PMID: 15377220

Ford99: Ford JD, Davin LB, Lewis NG (1999). "Plant lignans and health: cancer chemoprevention and biotechnological opportunities." Basic Life Sci 66;675-94. PMID: 10800470

Fujita99: Fujita M, Gang DR, Davin LB, Lewis NG (1999). "Recombinant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions." J Biol Chem 274(2);618-27. PMID: 9872995

Fuss03: Fuss E (2003). "Lignans in plant cell and organ cultures: An overview." Phytochemistry Reviews, 2, 307-320.

Halls02: Halls SC, Lewis NG (2002). "Secondary and quaternary structures of the (+)-pinoresinol-forming dirigent protein." Biochemistry 41(30);9455-61. PMID: 12135368

Halls04: Halls SC, Davin LB, Kramer DM, Lewis NG (2004). "Kinetic study of coniferyl alcohol radical binding to the (+)-pinoresinol forming dirigent protein." Biochemistry 43(9);2587-95. PMID: 14992596

Kim02c: Kim MK, Jeon JH, Davin LB, Lewis NG (2002). "Monolignol radical-radical coupling networks in western red cedar and Arabidopsis and their evolutionary implications." Phytochemistry 61(3);311-22. PMID: 12359517

Lewis99: Lewis NG, Davin LB, Sarkanen S (1999). "The nature and function of lignins." In: Comprehensive natural products chemistry Vol. 3: Barton Sir DHR, Nakanishi K. (eds.-in-chief), Carbohydrates and their derivatives including tannins, cellulose and related lignins. Amsterdam, New York: Elsevier 1999, 617-745.

MacRae84: MacRae WD, Towers GHN (1984). "Biological activities of lignans." Phytochemistry, 23(6), 1207-1220.

Moinuddin06: Moinuddin SG, Youn B, Bedgar DL, Costa MA, Helms GL, Kang C, Davin LB, Lewis NG (2006). "Secoisolariciresinol dehydrogenase: mode of catalysis and stereospecificity of hydride transfer in Podophyllum peltatum." Org Biomol Chem 4(5);808-16. PMID: 16493463

Saleem05: Saleem M, Kim HJ, Ali MS, Lee YS (2005). "An update on bioactive plant lignans." Nat Prod Rep 22(6);696-716. PMID: 16311631

Stafford00: Stafford E (2000). "The evolution of phenolics in plants." In: Recent advances in phytochemistry, Evolution of metabolic pathways (Romeo JT, Ibrahim R, Varin L, DeLuca V (eds.), Elsevier Science Ltd., 34, 25-55.

Umezawa91: Umezawa T, Davin LB, Lewis NG (1991). "Formation of lignans (-)-secoisolariciresinol and (-)-matairesinol with Forsythia intermedia cell-free extracts." J Biol Chem 266(16);10210-7. PMID: 2037574

vonHeimendahl05: von Heimendahl CB, Schafer KM, Eklund P, Sjoholm R, Schmidt TJ, Fuss E (2005). "Pinoresinol-lariciresinol reductases with different stereospecificity from Linum album and Linum usitatissimum." Phytochemistry 66(11);1254-63. PMID: 15949826

Xia01: Xia ZQ, Costa MA, Pelissier HC, Davin LB, Lewis NG (2001). "Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. Implications for human health protection." J Biol Chem 276(16);12614-23. PMID: 11278426

Youn05: Youn B, Moinuddin SG, Davin LB, Lewis NG, Kang C (2005). "Crystal structures of apo-form and binary/ternary complexes of Podophyllum secoisolariciresinol dehydrogenase, an enzyme involved in formation of health-protecting and plant defense lignans." J Biol Chem 280(13);12917-26. PMID: 15653677

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

Bayindir08: Bayindir U, Alfermann AW, Fuss E (2008). "Hinokinin biosynthesis in Linum corymbulosum Reichenb." Plant J 55(5);810-20. PMID: 18489708

Chu93a: Chu A, Dinkova A, Davin LB, Bedgar DL, Lewis NG (1993). "Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia." J Biol Chem 268(36);27026-33. PMID: 8262939

Gang99: Gang DR, Kasahara H, Xia ZQ, Vander Mijnsbrugge K, Bauw G, Boerjan W, Van Montagu M, Davin LB, Lewis NG (1999). "Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases." J Biol Chem 274(11);7516-27. PMID: 10066819

Gang99a: Gang DR, Costa MA, Fujita M, Dinkova-Kostova AT, Wang HB, Burlat V, Martin W, Sarkanen S, Davin LB, Lewis NG (1999). "Regiochemical control of monolignol radical coupling: a new paradigm for lignin and lignan biosynthesis." Chem Biol 6(3);143-51. PMID: 10074466

Hemmati07: Hemmati S, Schmidt TJ, Fuss E (2007). "(+)-Pinoresinol/(-)-lariciresinol reductase from Linum perenne Himmelszelt involved in the biosynthesis of justicidin B." FEBS Lett 581(4);603-10. PMID: 17257599

Katayama93: Katayama T, Davin LB, Chu A, Lewis NG (1993). "Novel benzylic ether reductions in lignan biogenesis in Forsythia intermedia." Phytochemistry, 33(3), 581-591.

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

Lewis99a: Lewis NG, Davin LB (1999). "Lignans: Biosynthesis and function." In: Comprehensive natural products chemistry Vol. 1: Barton Sir DHR, Nakanishi K. (eds.-in-chief), Carbohydrates Polyketides and other Secondary Metabolites including Fatty Acids and their Derivatives. Amsterdam, New York: Elsevier 1999, 639-712.

Min03: Min T, Kasahara H, Bedgar DL, Youn B, Lawrence PK, Gang DR, Halls SC, Park H, Hilsenbeck JL, Davin LB, Lewis NG, Kang C (2003). "Crystal structures of pinoresinol-lariciresinol and phenylcoumaran benzylic ether reductases and their relationship to isoflavone reductases." J Biol Chem 278(50);50714-23. PMID: 13129921

Nakatsubo08: Nakatsubo T, Mizutani M, Suzuki S, Hattori T, Umezawa T (2008). "Characterization of Arabidopsis thaliana pinoresinol reductase, a new type of enzyme involved in lignan biosynthesis." J Biol Chem 283(23);15550-7. PMID: 18347017

Sterjiades92: Sterjiades R, Dean JF, Eriksson KE (1992). "Laccase from Sycamore Maple (Acer pseudoplatanus) Polymerizes Monolignols." Plant Physiol 99(3);1162-8. PMID: 16668984

Umezawa90: Umezawa T, Davin LB, Lewis NG (1990). "Formation of the lignan, (-) secoisolariciresinol, by cell free extracts of Forsythia intermedia." Biochem Biophys Res Commun 171(3);1008-14. PMID: 2222424


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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 Fri Nov 28, 2014, BIOCYC13A.