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Diversity in lignan biosynthesis

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Abstract

Lignans are phenylpropanoid dimers, where the phenylpropane units are linked by the central carbon (C8) of their side chains. Ligans vary substantially in oxidation level, substitution pattern, and the chemical structure of their basic carbon framework. In addition to structural diversity, lignans show considerable diversity in terms of enantiomeric composition, biosynthesis, and phylogenetic distribution. In this review, these diversities are outlined and the phylogenetic distribution of plants producing 66 typical lignans is listed. The distribution is correlated with the putative biosynthetic pathways of the lignans and discussed from evolutionary aspects.

Abbreviations: SIRD – Secoisolariciresinol dehydrogenase; PLR – pinoresinol lariciresinol reductase; DP – dirigent protein

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References

  • Agata I, Hatano T, Nishibe S & Okuda T (1988) Rabdosiin, a new rosmarinic acid dimer with a lignan skeleton, from Rabdosia japonica. Chem. Pharm. Bull. 36: 3223–3225.

    Google Scholar 

  • Ayres DC & Loike JD (1990) Lignans Chemical, Biological and Clinical Properties. Cambridge University Press, Cambridge.

    Google Scholar 

  • Barrero AF, Haïdour A & Dorado MM (1994) Lignans from the wood of Abies pinsapo. J. Nat. Prod. 57: 713–719.

    Google Scholar 

  • Broomhead AJ, Rahman MMA, Dewick PM, Jackson DE & Lu-cas JA (1991) Matairesinol as precursor of Podophyllum lignans. Phytochemistry 30: 1489-1492.

    Google Scholar 

  • Charlton JL & Chee G-L (1997) Asymmetric synthesis of lignans using oxazolidinones as chiral auxiliaries. Can. J. Chem. 75: 1076–1083.

    Google Scholar 

  • Chen Y-g, Sun H-d, Xu Z-h & Qin G-w (2001) Studies on chemical constituents of Stellera chamejasma L. China J. Chin. Materia Medica 26: 477–479.

    Google Scholar 

  • Chu A, Dinkova A, Davin LB, Bedgar DL & Lewis NG (1993) Ste-reospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia. J. Biol. Chem. 268: 27026–27033.

    Google Scholar 

  • Cronquist A (1981) An integrated system of classification of flowering plants. Columbia University Press, New York.

    Google Scholar 

  • Cullmann F, Adam K-P & Becker H (1993) Bisbibenzyls and lignans from Pellia epiphylla. Phytochemistry 34: 831–834.

    Google Scholar 

  • Cullmann F, Adam K-P, Zapp J & Becker H (1996) Pelliatin, a mac-rocyclic lignan derivative from Pellia epiphylla. Phytochemistry 41: 611–615.

    Google Scholar 

  • Cullmann F, Schmidt A, Schuld F, Trennheuser ML & Becher H (1999a) Lignans from the liverworts Lepidozia incurvata, Chiloscyphus polyanthos and Jungermannia exsertifolia ssp. cordifolia. Phytochemistry 52: 1647–1650.

    Google Scholar 

  • Cullmann F & Becker H (1999b) Lignans from the liverwort Lepicolea ochroleuca. Phytochemistry 52: 1651–1656.

    Google Scholar 

  • Davin LB, Wang H-B, 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: 362–366.

    Google Scholar 

  • Della Greca M, Molinaro A, Monaco P & Previtera L (1993) Two new lignan glucosides from Arum italicum. Heterocycles 36: 2081–2086.

    Google Scholar 

  • Dewick PM (1989) Biosynthesis of lignans. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, Vol. 5 Structure elucidation (Part B) (pp. 459–503). Elsevier, Amsterdam.

    Google Scholar 

  • Dinkova-Kostova AT, Gang DR, Davin LB, Bedgar DL, Chu A & Lewis NG (1996) (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia. J. Biol. Chem. 271: 29473–29482.

    Google Scholar 

  • Erickson M & Miksche GE (1974) On the occurrence of lignin or polyphenols in some mosses and liverworts. Phytochemistry 13: 2295–2299.

    Google Scholar 

  • Erdtman H (1933) Dehydrierungen in der Coniferylreihe. (I). Dehydrodieugenol und Dehydrodiisoeugenol. Biochem. Z. 258: 172–180.

    Google Scholar 

  • Fonseca SF, de Paiva Campello J, Barata LES & Rúveda EA (1978) 13 C NMR spectral analysis of lignans from Araucaria angustifolia. Phytochemistry 17: 499–502.

    Google Scholar 

  • Fujita M, Gang DR, Davin LB & Lewis NG (1999) Recombin-ant pinoresinol-lariciresinol reductases from western red cedar (Thuja plicata) catalyze opposite enantiospecific conversions. J. Biol. Chem. 274: 618–627.

    Google Scholar 

  • Furuki T & Mizutani M(1994) Checklist of Japanese Hepaticae and Anthocerotae, 1993. Proc. Bryol. Soc. Japan 6: 75–83.

    Google Scholar 

  • Gibbs RD (1974) Chemotaxonomy of flowering plants, Vol 1. Constituents. McGill-Queen's University Press, Montreal.

    Google Scholar 

  • Gottlieb OR (1972) Chemosystematics of the Lauraceae. Phytochemistry 11: 1537–1570.

    Google Scholar 

  • Gottlieb OR (1978) Neolignans. Fortschr. Chem. Org. Naturst. 35: 1–72.

    Google Scholar 

  • Haworth RD (1936) Natural resins. Ann. Rep. Prog. Chem. 33: 266–279.

    Google Scholar 

  • Hostettler FD & Seikel MK (1969) Lignans of Ulmus thomasii heartwood-II. Lignans related to thomasic acid. Tetrahedron 25: 2325–2337.

    Google Scholar 

  • Ishii H, Ishikawa T, Mihara M & Akaike M (1983) Studies on the chemical constituents of Rutaceous plants. XLVIII. The chemical constituents of Xanthoxylum ailanthoides Sieb. et Zucc. [Fagara ailanthoides (Sieb. et Zucc.) Engl.]. (3) Isolation of the chemical constituents of the bark. Yakugaku Zasshi 103: 279–292.

    Google Scholar 

  • Jackson DE & Dewick PM (1984a) Biosynthesis of Podophyllum lignans-I. Cinnamic acid precursors of podophyllotoxin in Podophyllum hexandrum. Phytochemistry 23: 1029–1035.

    Google Scholar 

  • Jackson DE & Dewick PM (1984b) Biosynthesis of Podophyllum lignans-II. Interconversions of aryltetralin lignans in Podophyl-lum hexandrum. Phytochemistry 23: 1037–1042.

    Google Scholar 

  • Jiao Y, Davin LB & Lewis NG (1998) Furanofuran lignan meta-bolism as a function of seed maturation in Sesamum indicum: Methylenedioxy bridge formation. Phytochemistry 49: 387–394.

    Google Scholar 

  • Jiang Z-H, Tanaka T & Kouno I (1996) Chilianthins A-F, six triter-pene esters having dimeric structures from Rhoiptelea chiliantha Diels et Hand.-Mazz. Chem. Pharm. Bull. 44: 1669–1675.

    Google Scholar 

  • Kamil WM & Dewick PM (1986a) Biosynthesis of the lignans á-and â-peltatin. Phytochemistry 25: 2089–2092.

    Google Scholar 

  • Kamil WM & Dewick PM (1986b) Biosynthetic relationship of aryltetralin lactone lignans to dibenzylbutyrolactone lignans. Phytochemistry 25: 2093–2102.

    Google Scholar 

  • Katayama T, Davin LB & Lewis NG (1992) An extraordinary accumulation of (-)-pinoresinol in cell-free extracts of For-sythia intermedia: evidence for enantiospecific reduction of (+)-pinoresinol. Phytochemistry 31: 3875–3881

    Google Scholar 

  • Katayama T, Davin LB, Chu A & Lewis NG (1993) Novel benzylic ether reductions in lignan biogenesis in Forsythia intermedia. Phytochemistry 33: 581–591.

    Google Scholar 

  • Katayama T, Masaoka T & Yamada H (1997) Biosynthesis and stereochemistry of lignans in Zanthoxylum ailanthoides I. (+)-Lariciresinol formation by enzymatic reduction of ( ±)-pinoresinols. Mokuzai Gakkaishi 43: 580–588.

    Google Scholar 

  • Kato M (1997) Diversity and evolution of land plants. Shokabo, Tokyo.

    Google Scholar 

  • Kato MJ, Chu A, Davin LB & Lewis NG (1998) Biosynthesis of antioxidant lignans in Sesamum indicum seeds. Phytochemistry 47: 583–591.

    Google Scholar 

  • Kawai S, Sugishita K & Ohashi H (1999) Identification of Thuja occidentalis lignans and its biosynthetic relationship. Phytochemistry 51: 243–247.

    Google Scholar 

  • Khamlach K, Dhal R & Brown E (1989) Total syntheses of (-)-trachelogenin, (-)-nortrachelogenin and (+)-wikstromol. Tetrahedron Lett. 30: 2221–2224.

    Google Scholar 

  • Kitagawa S, Nishibe S, Benecke R & Thieme H (1988) Phenolic compounds from For s yt hi a leaves. II. Chem. Pharm. Bull. 36: 3667–3670.

    Google Scholar 

  • Kobayashi W, Miyase T, Suzuki S, Noguchi H & Chen X-M (2000) Oligosaccharide esters from the roots of Polygala arillata. J. Nat. Prod. 63: 1066–1069.

    Google Scholar 

  • Kramer KU & Green PS (1990) The families and genera of vascular plants, Vol 1, Pteridophytes & Gymnosperms. Springer-Verlag, Berlin.

    Google Scholar 

  • Kuhlmann S, Kranz K, Lücking B, Alfermann AW & Petersen M (2002) Aspects of cytotoxic lignan biosynthesis in suspension cultures of Linum nodiflorum. Phytochemistry Rev. 1: 37–43.

    Google Scholar 

  • Lewis NG & Davin LB (1999) Lignans: Biosynthesis and function. In: Sankawa U (ed) Comprehensive Natural Products Chemistry, Vol 1 (pp. 639-712). Elsevier, Amsterdam.

    Google Scholar 

  • Lin L-Z, Hu S-F, Chai H-B, Pengsuparp T, Pezzuto JM, Cordell GA & Ruangrungsi N (1995) Lycorine alkaloids from Hymenocallis littoralis. Phytochemistry 40: 1295–1298.

    Google Scholar 

  • Lin RC, Skaltsounis A-L, Seguin E, Tillequin F & Koch M (1994) Phenolic constituents of Selaginella doederleinii. Planta Med. 60: 168–170.

    Google Scholar 

  • McCredie RS, Ritchie E & Taylor WC (1969) Constituents of Eupo-matia species. The structure and synthesis of eupomatene, a lignan of novel type from Eupomatia laurina R. Br. Aust. J. Chem. 22: 1011–1032.

    Google Scholar 

  • MacRae WD & Towers GHN (1984) Biological activities of lignans. Phytochemistry 23: 1207–1220.

    Google Scholar 

  • Martini U, Zapp J & Becker H (1998) Lignans from the liverwort Bazzania trilobata. Phytochemistry 49: 1139–1146.

    Google Scholar 

  • Mikame K, Sakakibara N, Umezawa T & Shimada M (2002) Lignans of Linum flavum var. compactum. J. Wood Sci. 48: 440–445.

    Google Scholar 

  • Miksche GE & Yasuda S (1978) Lignin of 'giant' mosses and some related species. Phytochemistry 17: 503–504.

    Google Scholar 

  • Miyauchi T & Ozawa S (1998) Formation of (+)-eudesmin in Magnolia kobus DC. var. borealis SARG. Phytochemistry 47: 665–670.

    Google Scholar 

  • Moinuddin SGA, Hishiyama S, Cho M-H, Davin LB & Lewis NG (2003) Synthesis and chiral HPLC analysis of the dibenzyl-tetrahydrofuran lignans, larreatricins, 8 -epi-larreatricins, 3,3-didemethoxyverrucosins and meso-3,3-didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence for regio-specific control of coupling. Org. Biomol. Chem. 1: 2307–2313.

    Google Scholar 

  • Molog GA, Empt U, Kuhlmann S, van Uden W, Pras N, Alfermann AW & Petersen M(2001) Deoxypodophyllotoxin 6-hydroxylase, a cytochrome P450 monooxygenase from cell cultures of Linum flavum involved in the biosynthesis of cytotoxic lignans. Planta 214: 288–294.

    Google Scholar 

  • Moss GP (2000) Nomenclature of lignans and neolignans (IUPAC Recommendations 2000). Pure Appl. Chem. 72: 1493–1523.

    Google Scholar 

  • Nabeta K, Nakahara K, Yonekubo J, Okuyama H & Sasaya T (1991) Lignan biosynthesis in Larix leptolepis callus. Phytochemistry 30: 3591–3593.

    Google Scholar 

  • Nishibe S, Sakushima A, Kitagawa S, Klimek B, Benecke R & Thieme H (1988) Phenolic compounds from For s yt hi a leaves (III). On the comparison of constituents between hybrid and parents. Shoyakugaku Zasshi 42: 324–328.

    Google Scholar 

  • Okunishi T, Umezawa T & Shimada M (2000) Enantiomeric com-positions and biosynthesis of Wikstroemia sikokiana lignans. J. Wood Sci. 46: 234–242.

    Google Scholar 

  • Okunishi T, Umezawa T & Shimada M (2001) Isolation and en-zymatic formation of lignans of Daphne genkwa and Daphne odora. J. Wood Sci. 47: 383–388.

    Google Scholar 

  • Okunishi T, Sakakibara N, Suzuki S, Umezawa T & Shimada M (2004) Stereochemistry of matairesinol formation by Daphne secoisolariciresinol dehydrogenase. J. Wood Sci. 50: 77–81.

    Google Scholar 

  • Ozawa S, Davin LB & Lewis NG (1993) Formation of (-)-arctigenin in Forsythia intermedia. Phytochemistry 32: 643–652.

    Google Scholar 

  • Petersen M & Alfermann AW (2001) The production of cytotoxic lignans by plant cell cultures. Appl. Microbol. Biotechnol. 55: 135–142.

    Google Scholar 

  • Rahman MMA, Dewick PM, Jackson DE & Lucas JA (1990) Lig-nans of Forsythia intermedia. Phytochemistry 29: 1971–1980.

    Google Scholar 

  • Sakakibara I, Ikeya Y, Hayashi K & Mitsuhashi H (1992) Three phenyldihydronaphthalene lignanamides from fruits of Cannabis sativa. Phytochemistry 31: 3219–3223.

    Google Scholar 

  • Sakakibara N, Suzuki S, Umezawa T & Shimada M (2003) Biosyn-thesis of yatein in Anthriscus sylvestris. Org. Biomol. Chem. 1: 2474–2485.

    Google Scholar 

  • Scher JM, Zapp J & Becker H (2003) Lignan derivatives from the liverwort Bazzania trilobata. Phytochemistry 62: 769–777.

    Google Scholar 

  • Suzuki H, Lee K-H, Haruna M, Iida T, Ito K & Huang H-C (1982) (+)-Arctigenin, a lignan from Wikstroemia indica. Phytochemistry 21: 1824–1825.

    Google Scholar 

  • Suzuki S, Umezawa T & Shimada M (1998) Stereochemical difference in secoisolariciresinol formation between cell-free extracts from petioles and from ripening seeds of Arctium lappa L. Biosci. Biotech. Biochem. 62: 1468–1470.

    Google Scholar 

  • Suzuki S, Umezawa T & Shimada M (2001) Norlignan biosynthesis in Asparagus officinalis. J. Chem. Soc. Perkin Trans. 1 3252–3257.

    Google Scholar 

  • Suzuki S, Nakatsubo T, Umezawa T & Shimada M (2002a) First in vitro norlignan formation with Asparagus officinalis enzyme preparation. Chem. Commun. 1088–1089.

  • Suzuki S, Umezawa T & Shimada M (2002b) Stereochemical diversity in lignan biosynthesis of Arctium lappa L. Biosci. Biotech. Biochem. 66: 1262–1269.

    Google Scholar 

  • Suzuki S, Sakakibara N, Umezawa T & Shimada M (2002c) Survey and enzymatic formation of lignans of Anthriscus sylvestris. J. Wood Sci. 48: 536–541.

    Google Scholar 

  • Takaku N, Choi D-H, Mikame K, Okunishi T, Suzuki S, Ohashi H, Umezawa T & Shimada M (2001) Lignans of Chamaecyparis obtusa. J. Wood Sci. 47: 476–482.

    Google Scholar 

  • Tandon S & Rastogi RP (1976) Wikstromol, a new lignan from Wikstroemia viridiflora. Phytochemistry 15: 1789–1791.

    Google Scholar 

  • Tazaki H (2000) Biosynthetic studies on secondary metabolites of in vitro cultured liverworts. Nippon Nogeikagaku Kaishi 74: 137–143.

    Google Scholar 

  • Tazaki H, Hayashida T, Ishikawa F, Taguchi D, Takasawa T & Na-beta K (1999) Lignan biosynthesis in liverworts Jamesoniella. autumnalis and Lophocolea heterophylla. Tetrahedron Lett. 40: 101–104.

    Google Scholar 

  • Tazaki H, Ito M, Miyoshi M, Kawabata J, Fukushi E, Fujita T, Mo-touri M, Furuki T & Nabeta K (2002) Subulatin, an antioxidic caffeic acid derivative isolated from the in vitro cultured liver-worts, Jungermannia subulata, Lophocolea heterophylla,and Scapania parvitexta. Biosci. Biotechnol. Biochem. 66: 255–261.

    Google Scholar 

  • Tiwari AK, Srinivas PV, Kumar SP & Rao JM (2001) Free radical scavenging active components from Cedrus deodara. J. Agric. Food Chem. 49: 4642–4645.

    Google Scholar 

  • Umezawa T (1996) Biological activity and biosynthesis of lignans. Mokuzai Gakkaishi 42: 911–920.

    Google Scholar 

  • Umezawa T (1997) Lignans. In: Higuchi T (ed) Springer Series in Wood Science, Biochemistry and Molecular Biology of Wood (pp. 181–194). Springer-Verlag, Berlin.

    Google Scholar 

  • Umezawa T (2000) Chemistry of extractives. In Hon DN-S & Shiraishi N (eds) Wood and Cellulosic Chemistry 2nd Ed. revised and expanded (pp. 213–241). Marcel Dekker, New York.

    Google Scholar 

  • Umezawa T (2001) Biosynthesis of lignans and related phenylpro-panoid compounds. Regulation of Plant Growth & Development 36: 57–67.

    Google Scholar 

  • Umezawa T (2003) Phylogenetic distribution of lignan producing plants. Wood Research 90: 27–110.

    Google Scholar 

  • Umezawa T, Davin LB & Lewis NG (1990a) Formation of the lig-nan, (-) secoisolariciresinol, by cell free extracts of For s yt hi a intermedia. Biochem. Biophys. Res. Commun. 171: 1008–1014.

    Google Scholar 

  • Umezawa T, Davin LB, Yamamoto E, Kingston DGI & Lewis NG (1990b) Lignan biosynthesis in Forsythia species. J. Chem. Soc. Chem. Commun.: 1405–1408.

  • Umezawa T, Davin LB & Lewis NG (1991) Formation of lig-nans (-)-secoisolariciresinol and (-)-matairesinol with For s yt hi a intermedia cell-free extracts. J. Biol. Chem. 266: 10210–10217.

    Google Scholar 

  • Umezawa T, Isohata T, Kuroda H, Higuchi T & Shimada M (1992) Chiral HPLC and LC-MS analysis of several lignans. In: Kuwa-hara M, Shimada M (eds) Biotechnology in Pulp and Paper Industry (pp. 507–512). Uni Publ., Tokyo.

    Google Scholar 

  • Umezawa T, Kuroda H, Isohata T, Higuchi T & Shimada M (1994) Enantioselective lignan synthesis by cell-free extracts of Forsythia koreana. Biosci. Biotech. Biochem. 58: 230–234.

    Google Scholar 

  • Umezawa T & Shimada M (1996a) Enantiomeric composition of (-)-pinoresinol, (+)-matairesinol and (+)-wikstromol isolated from Wikstroemia sikokiana. Mokuzai Gakkaishi 42: 180–185.

    Google Scholar 

  • Umezawa T & Shimada M (1996b) Formation of the lignan (+)-secoisolariciresinol by cell-free extracts of Arctium lappa. Biosci. Biotech. Biochem. 60: 736–737.

    Google Scholar 

  • Umezawa T, Okunishi T & Shimada M (1997a) Stereochemical diversity in lignan biosynthesis. Wood Research 84: 62–75.

    Google Scholar 

  • Umezawa T, Okunishi T & Shimada M (1997b) Mechanisms of lignan biosynthesis. Annual Rep. Interdiscipl. Res. Inst. Environ. Sci. 16: 65–71.

    Google Scholar 

  • Umezawa T, Okunishi T, Mikame K, Suzuki S, Liswidowati, Wasrin Syafii & Shimada M (1998) Mechanisms of lignan biosynthesis, part II. Annual Rep. Interdiscipl. Res. Inst. Environ. Sci. 17: 29–36.

    Google Scholar 

  • Whiting DA (1985) Lignans and neolignans. Nat. Prod. Rep. 2: 191–211.

    Google Scholar 

  • Xia Z-Q, Costa MA, Proctor J, Davin LB & Lewis NG (2000) Dirigent-mediated podophyllotoxin biosynthesis in Linum flavum and Podophyllum peltatum. Phytochemistry 55: 537–549.

    Google Scholar 

  • Xia Z-Q, Costa MA, Pélissier HC, Davin LB & Lewis NG (2001) Secoisolariciresinol dehydrogenase purification, cloning, and functional expression. J. Biol. Chem. 276: 12614–12623.

    Google Scholar 

  • Yamamoto H, Inoue K & Yazaki K (2000) Caffeic acid oligomers in Lithospermum erythrorhizon cell suspension cultures. Phyto-chemistry 53: 651–657.

    Google Scholar 

  • Zhang H-J, Tamez PA, Hoang VD, Tan GT, Hung NV, Xuan LT, Huong LM, Cuong NM, Thao DT, Soejarto DD, Fong HHS & Pezzuto JM (2001) Antimalarial compounds from Rhaphido-phora decursiva. J. Nat. Prod. 64: 772–777.

    Google Scholar 

  • Zinsmeister HD, Becker H & Eicher T (1991) Bryophytes, a source of biologically active, naturally occurring material? Angew. Chem. Int. Ed. Engl. 30: 130–147.

    Google Scholar 

  • Xu Z-h, Qin G-w, Li X-y & Xu R-s (2001) New biflavanones and bioactive compounds from Stellera chamaejasme L. Acta Pharmac. Sin. 36: 668–671.

    Google Scholar 

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    Toshiaki Umezawa

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Umezawa, T. Diversity in lignan biosynthesis. Phytochemistry Reviews 2, 371–390 (2003). https://doi.org/10.1023/B:PHYT.0000045487.02836.32

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