5196Accesses
195Citations
3Altmetric
Abstract
Lignans and norlignans constitute abundant classes of phenylpropanoids. Biosynthesis of these compounds has received widespread interest, mainly because they have various clinically important biological activities. In addition, lignans and norlignans are often biosynthesized and deposited in significant amounts in the heartwood region of trees as a metabolic event of heartwood formation, probably preventing heart rot by heart-rot fungi. Furthermore, biosynthetic reactions of lignans and norlignans involve unique stereochemical properties that are of great interest in terms of bioorganic chemistry and are expected to provide a model for biomimetic chemistry and its application. We outline the recent advances in the study of lignan and norlignan biosynthesis.
Article PDF
Similar content being viewed by others
References
Umezawa T (2003) Diversity in lignan biosynthesis. Phytochem Rev 2:371–390
Moss GP (2000) Nomenclature of lignans and neolignans (IUPAC Recommendations 2000). Pure Appl Chem 72:1493–1523
Umezawa T (2003) Phylogenetic distribution of lignan producing plants. Wood Res 90:27–110
Suzuki S, Umezawa T, Shimada M (2001) Norlignan biosynthesis inAsparagus officinalis L.: the norlignan originates from two nonidentical phenylpropane units. J Chem Soc Perkin Trans 1:3252–3257
Umezawa T (2005) Biosynthesis of lignans, lignins, and norlignans. Kagaku to Seibutsu 43:461–467
Sakakibara N, Nakatsubo T, Suzuki S, Shibata D, Shimada M, Umezawa T (2007) Metabolic analysis of the cinnamate/monolignol pathway inCarthamus tinctorius seeds by a stable-isotope-dilution method. Org Biomol Chem 5:802–815
Chiang VL (2006) Monolignol biosynthesis and genetic engineering of lignin in trees, a review. Environ Chem Lett 4:143–146
Umezawa T, Okunishi T, Shimada M (1997) Stereochemical diversity in lignan biosynthesis. Wood Res 84:62–75
Akiyama T, Magara K, Matsumoto Y, Meshitsuka G, Ishizu A, Ludquist K (2000) Proof of the presence of racemic forms of arylglycerol-β-aryl ether structure in lignin: studies on the stereo structure of lignin by ozonation. J Wood Sci 46:414–415
Paré PW, Wang H-B, Davin LB, Lewis NG (1994) (+)-Pinoresinol synthase: a stereoselective oxidase catalysing 8,8′-lignan formation inForsythia intermedia. Tetrahedron Lett 35:4731–4734
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
Halls SC, Lewis NG (2002) Secondary and quaternary structures of the (+)-pinoresinol-forming dirigent protein. Biochemistry 41:9455–9461
Halls SC, Davin LB, Kramer DM, Lewis NG (2004) Kinetic study of coniferyl alcohol radical binding to the (+)-pinoresinol forming dirigent protein. Biochemistry 43:2587–2595
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 6:143–151
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 123:453–461
Kim MK, Jeon J-H, Fujita M, Davin LB, Lewis NG (2002) The western red cedar (Thuja plicata) 8-8′ DIRIGENT family displays diverse expression patterns and conserved monolignol coupling specificity. Plant Mol Biol 49:199–214
Ralph S, Park J-Y, Bohlmann J, Mansfield SD (2006) Dirigent proteins in conifer defense: gene discovery, phylogeny, and differential wound-and insect-induced expression of a family of DIR and DIR-like genes in spruce (Picea spp.). Plant Mol Biol 60:21–40
Wang Y, Nowak G, Culley D, Hadwiger LA, Fristensky B (1999) Constitutive expression of pea defense gene DRR206 confers resistance to blackleg (Leptosphsrtis maculans) disease in transgenic canola (Brassica napus). Mol Plant Microbe Interact 12:410–418
Burlat V, Kuwan M, Davin LB, Lewis NG (2001) Dirigent proteins and dirigent sites in lignifying tissues. Phytochemistry 57:883–897
Takabe K, Fujita M, Harada H, Saiki H (1981) Lignification process of Japanese black pine (Pinus thunbergii Parl.) tracheids. Mokuzai Gakkaishi 12:813–820
Terashima N, Fukushima K, Takabe K (1986) Heterogeneity in formation of lignin VIII. An autoradiographic study on the formation of guaiacyl and syringyl lignin inMagnolia kobus DC. Holzforschung 40:101–105
Fukushima K, Terashima N (1991) Heterogeneity in formation of lignin XIV. Formation and structure of lignin in differentiating xylem ofGinkgo biloba. Holzforschung 45:87–94
Davin LB, Lewis NG (2005) Lignin primary structures and dirigent sites. Curr Opin Biotech 16:407–415
Hatfield R, Vermerris W (2001) Lignin formation in plants. The dilemma of linkage specificity. Plant Physiol 126:1351–1357
Boerjan W, Ralph J, Baucher M (2003) Lignin biosynthesis. Annu Rev Plant Biol 54:519–546
Ralph J, Lundquist K, Brunow G, Lu F, Kim H, Schatz PF, Marita JM, Hatfield RD, Ralph SA, Chirstensen JH, Boerjan W (2004) Lignins: natural polymers from oxidative coupling of 4-hydroxyphenylpropanoids. Phytochem Rev 3:29–60
Morreel K, Ralph J, Lu F, Goeminne G, Busson R, Herdewijn P, Goeman JL, Van der Eycken J, Boerjan W, Messens E (2004) Phenolic profiling of caffeic acidO-methyltransferase-deficient poplar reveals novel benzodioxane oligolignols. Plant Physiol 136:4023–4036
Umezawa T, Davin LB, Lewis NG (1990) Formation of the lignan, (−)-secoisolariciresinol, by cell free extracts ofForsythia intermedia. Biochem Biophys Res Commun 171:1008–1014
Katayama T, Davin LB, Lewis NG (1992) An extraordinary accumulation of (−)-pinoresinol in cell-free extracts ofForsythia intermedia: evidence for enantiospecific reduction of (+)-pinoresinol. Phytochemistry 31:3875–3881
Katayama T, Davin LB, Chu A, Lewis NG (1993) Novel benzylic ether reductions in lignan biogenesis inForsythia intermedia. Phytochemistry 33:581–591
Umezawa T, Kuroda H, Isohata T, Higuchi T, Shimada M (1994) Enantioselective lignan synthesis by cell-free extracts ofForsythia koreana. Biosci Biotech Biochem 58:230–234
Umezawa T, Shimada M (1996) Formation of the lignan (+)-secoisolariciresinol by cell-free extracts ofArctium lappa. Biosci Biotech Biochem 60:736–737
Suzuki S, Umezawa T, Shimada M (1998) Stereochemical difference in secoisolariciresinol formation between cell-free extracts from petioles and from ripening seeds ofArctium lappa L. Biosci Biotech Biochem 62:1468–1470
Suzuki S, Umezawa T, Shimada M (2002) Stereochemical diversity in lignan biosynthesis ofArctium lappa L. Biosci Biotech Biochem 66:1262–1269
Katayama T, Masaoka T, Yamada H (1997) Biosynthesis and stereochemistry of lignans inZanthoxylum ailanthoides I. (+)-Lariciresinol formation by enzymatic reduction of (±)-pinoresinols. Mokuzai Gakkaishi 43:580–588
Suzuki S, Sakakibara N, Umezawa T, Shimada M (2002) Survey and enzymatic formation of lignans ofAnthriscus sylvestris. J Wood Sci 48:536–541
Xia Z-Q, Costa MA, Proctor J, Davin LB, Lewis NG (2000) Dirigent-mediated podophyllotoxin biosynthesis inLinum flavum andPodophyllum peltatum. Phytochemistry 55:537–549
von Heimendahl CBI, Schäfer KM, Eklund P, Sjöholm R, Schmidt TJ, Fuss E (2005) Pinoresinol-lariciresinol reductases with different stereospecificity fromLinum album andLinum usitatissimum. Phytochemistry 66:1254–1263
Okunishi T, Umezawa T, Shimada M (2001) Isolation and enzymatic formation of lignans ofDaphne genkwa andDaphne odora. J Wood Sci 47:383–388
Chu A, Dinkova A, Davin LB, Bedgar DL, Lewis NG (1993) Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases fromForsythia intermedia. J Biol Chem 268:27026–27033
Dinkova-Kostova AT, Gang DR, Davin LB, Bedgar DL, Chu A, Lewis NG (1996) (+)-Pinoresinol/(+)-lariciresinol reductase fromForsythia intermedia. J Biol Chem 271:29473–29482
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 274:618–627
Min T, Kasahara H, Bedgar DL, Youn B, Lawrence PK, Gang DR, Halls SC, Park HJ, 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 278:50714–50723
Umezawa T, Davin LB, Yamamoto E, Kingston DGI, Lewis NG (1990) Lignan biosynthesis in Forsythia species. J Chem Soc Chem Commun 1405–1408
Umezawa T, Davin LB, Lewis NG (1991) Formation of lignans (−)-secoisolariciresinol and (−)-matairesinol withForsythia intermedia cell-free extracts. J Biol Chem 266:10210–10217
Okunishi T, Sakakibara N, Suzuki S, Umezawa T, Shimada M (2004) Stereochemistry of matairesinol formation byDaphne secoisolariciresinol dehydrogenase. J Wood Sci 50:77–81
Umezawa T (2001) Biosynthesis of lignans and related phenylpropanoid compounds. Regul Plant Growth Dev 36:57–67
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
Youn B, Moinuddin SGA, Davin LB, Lewis NG (2005) Cyrstal structures of apo-form and binary/ternary complexes ofPodophyllum secoisolariciresinol dehydrogenase, an enzyme involved in formation of health-protecting and plant defense lignans. J Biol Chem 280:12917–12926
Moinuddin SGA, Youn B, Bedgar DL, Costa MA, Helms GL, Kang CH, Davin LB, Lewis NG (2006) Secoisolariciresinol dehydrogenase: mode of catalysis and stereospecificity of hydride transfer inPodophyllum peltatum. Org Biol Chem 4:808–816
Dewick PM (1989) Biosynthesis of lignans. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 5. Structure elucidation (part B). Elsevier, Amsterdam, pp 459–503
Broomhead AJ, Rahman MMA, Dewick PM, Jackson DE, Lucas JA (1991) Matairesinol as precursor ofPodophyllum lignans. Phytochemistry 30:1489–1492
Sakakibara N, Suzuki S, Umezawa T, Shimada M (2003) Biosynthesis of yatein inAnthriscus sylvestris. Org Biomol Chem 1:2474–2485
Petersen M, Alfermann AW (2001) The production of cytotoxic lignans by plant cell cultures. Appl Microbiol Biotechnol 55:135–142
Kuhlmann S, Kranz K, Lücking B, Alfermann AW, Petersen M (2002) Aspects of cytotoxic lignan biosynthesis in suspension cultures ofLinum nodiflorum. Phytochem Rev 1:37–43
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 ofLinum flavum involved in the biosynthesis of cytotoxic lignans. Planta 214:288–294
Kranz K, Petersen M (2003)β-Peltatin 6-O-methyltransferase from suspension cultures ofLinum nodiflorum. Phytochemistry 64:453–458
Umezawa T, Li L, Suzuki S, Sakakibara N, Nakatsubo T, Chiang VL (2004) A novel O-methyltransferase catalyzing a regioselective methylation of lignan. Proceedings of the 49th Lignin Symposium, Tsukuba, Japan, pp 33–36
Puri SC, Nazir A, Chawla R, Arora R, Siyaz-ul-Hasan S, Amna T, Ahmed B, Verma V, Singh S, Sagar R, Sharma A, Kumar R, Sharma RK, Qazi GN (2006) The endophytic fungusTrametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122:494–510
Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates fromPodophyllum peltatum produce podophyllotoxin. J Nat Prod 69:1121–1124
Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production byTaxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216
Arroo RRJ, Alfermann AW, Medarde M, Petersen M, Pras N, Woolley JG (2002) Plant cell factories as a source for anti-cancer lignans. Phytochem Rev 1:27–35
Fuss E (2003) Lignans in plant cell and organ cultures: an overview. Phytochem Rev 2:307–320
Kato MJ, Chu A, Davin LB, Lewis NG (1998) Biosynthesis of antioxidant lignans inSesamum indicum seeds. Phytochemistry 47:583–591
Jiao Y, Davin LB, Lewis NG (1998) Furanofuran lignan metabolism as a function of seed maturation inSesamum indicum: methylenedioxy bridge formation. Phytochemistry 49:387–394
Ono E, Nakai M, Fukui Y, Tominori N, Fukuchi-Mizunati M, Saito M, Satake H, Tanaka T, Katsuta M, Umezawa T, Tanaka Y (2006) Formation of two methylenedioxy bridges by aSesamum CYP81Q protein yielding a furofuran lignan, (+)-sesamin. Proc Natl Acad Sci USA 103:10116–10121
Gottlieb OR (1972) Chemosystematics of the Lauraceae. Phytochemistry 11:1537–1570
Moinuddin SGA, Hishiyama S, Cho M-H, Davin LB, Lewis NG (2003) Synthesis and chiral HPLC analysis of the dibenzyltetrahydrofuran lignans, larreatricins, 8′-epi-larreatricins, 3,3′-didemethoxyverrucosins andmeso-3,3′-didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence for regiospecific control of coupling. Org Biomol Chem 1:2307–2313
Lopes NP, Yoshida M, Kato MJ (2004) Biosynthesis of tetrahydrofuran lignans inVirola surinamensis. Brazil J Pharm Sci 40:53–57
Koeduka T, Fridman E, Gang DR, Vassão DG, Jackson RL, Kish CM, Orlova I, Spassova SM, Lewis NG, Noel JP, Baiga TJ, Dudareva N, Pichersky E (2006) Eugenol and isoeugenol, characteristic aromatic constituents of spices are biosynthesized via reduction of a coniferyl alcohol ester. Proc Natl Acad Sci USA 103:10128–10133
Vassão DG, Gang DR, Koeduka T, Jackson B, Pichersky E, Davin LB, Lewis NG (2006) Chavicol formation in sweet basil (Ocimum basilicum): cleavage of an esterified C9 hydroxyl group with NAD(P)H-dependent reduction. Org Biomol Chem 4:2733–2744
Castro MA, Gordaliza M, Miguel del Corral J, San Fericiano A (1996) The distribution of lignanoids in the order Coniferae. Phytochemistry 41:995–1011
Erdtman H, Harmatha J (1979) Phenolic and terpenoid heartwood constituents ofLibocedrus yateensis. Phytochemistry 18:1495–1500
Begley MJ, Davies RV, Henley-Smith P, Whiting DA (1973) Constitution of sequirin-D (Sequoia sempervirens), a novel dihydronaphtalene norlignan. J Chem Soc Chem Commun 649–650
Begley MJ, Davies RV, Henley-Smith P, Whiting DA (1978) The constitution of (1R)-sequirin-D (Sequoia sempervirens), a biogenetically novel norlignan, by direct X-ray analysis. J Chem Soc Perkin Trans 1 750–754
Plieninger H, Schwarz B, Jaggy H, Huber-Patz U, Rodewald H, Irngartinger H, Weinges K (1986) Natural products from medicinal plants, XXIV-isolation, structure determination and synthesis of (Z,Z)-4-4′-(1,4-pentadiene-1,5-diyl) diphenol, an unusual natural product from the leaves of the Ginkgo tree (Ginkgo biloba L.). Liebigs Ann Chem 1772–1778
Daniels P, Erdtman H, Nishimura K, Norin T (1972) Athrotaxin, a C17-phenolic constituent fromAthrotaxis selaginoides Don. J Chem Soc Chem Commun 246–247
Enoki A, Takahama S, Kitao K (1977) The extractives of Metasekoia,Metasequoia glyptostroboides Hu et Cheng. I. Mokuzai Gakkaishi 23:579–586
Enoki A, Takahama S, Kitao K (1977) The extractives of Metasekoia,Metasequoia glyptostroboides Hu et Cheng. II. Mokuzai Gakkaishi 23:587–593
Tsui Y, Brown GD (1996) (+)-Nyasol fromAsparagus cochinchinensis. Phytochemistry 43:1413–1415
Nikaido T, Ohmoto T, Noguchi H, Kinoshita T, Saitoh H, Sankawa U (1981) Inhibitors of cyclic AMP phosphodiesterase in medicinal plants. Planta Medica 43:18–23
Terada K, Kamisako W (1999)1H-NMR and mass spectral study of a D-enriched acetylenic norlignan, asparenyol, from cultured cells ofAsparagus officinalis. Biol Pharm Bull 22:561–566
Abegaz BM, Ngadjui BT, Bezabih M, Mdee LK (1999) Novel natural products from marketed plants of eastern and southern Africa. Pure Appl Chem 71:919–926
Kinjo J, Furusawa J, Nohara T (1985) Two novel aromatic glycosides, pueroside-A and-B, fromPuerariae radix. Tetrahedron Lett 26:6101–6102
Shirataki Y, Tagaya Y, Yokoe I, Komatsu M (1987) Sophoraside A, a new aromatic glycoside from the roots ofSophora japonica. Chem Pharm Bull 35:1637–1640
Nohara T, Kinjo J, Furusama J, Sakai Y, Inoue M, Shirataki Y, Ishibashi Y, Yokoe I, Komatsu M (1993) But-2-enolides fromPueraria lobata and revised structures of puerosides A, B and sophoroside A. Phytochemistry 31:1207–1210
Kogiso S, Hosozawa S, Wada K, Munakata K (1974) Daphneolone in roots ofDaphne odora. Phytochemistry 13:2332–2334
Beracierta AP, Whiting DA (1978) Stereoselective total syntheses of the (±)-di-O-methyl ethers of agatharesinol, sequirin-A, and hinokiresinol, and of (±)-tri-O-methylsequrin-E, characteristic norlignans of Coniferae. J Chem Soc Perkin Trans 1 1257–1263
Birch AJ, Liepa AJ (1978) Biosynthesis. In: Rao CBS (ed) Chemistry of lignans. Andhra University Press, Andhra Pradesh, pp 307–327
Suzuki S, Nakatsubo T, Umezawa T, Shimada M (2002) First in vitro norlignan formation withAsparagus officinalis enzyme preparation. Chem Commun 1088–1089
Suzuki S, Yamamura M, Shimada M, Umezawa T (2004) A heart-wood norlignan, (E)-hinokiresinol, is formed from 4-coumaryl 4-coumarate by aCryptomeria japonica enzyme preparation. Chem Commun 2838–2839
Zhang YM, Tan NH, He M, Lu Y, Shang SQ, Zheng QT (2004) Sequosempervirin A, a novel spirocyclic compounds fromSequoia sempervirens. Tetrahedron Lett 45:4319–4321
Davin LB, Lewis NG (2005) Dirigent phenoxy radical coupling: advances and challenges. Curr Opin Biotechnol 16:398–406
Imai T, Nomura M, Fukushima K (2006) Evidence for involvement of the phenylpropanoid pathway in the biosynthesis of the norlignan agatharesinol. J Plant Physiol 163:483–487
Imai T, Nomura M, Matsushita Y, Fukushima K (2006) Hinokiresinol is not a precursor of agatharesinol in the norlignan biosynthetic pathway in Japanese cedar. J Plant Physiol 163:1221–1228
Imai T, Takino M, Itoh, E, Fukushima K (2006) In vitro formation of Sequirin-C by a microsomal fraction prepared fromCryptomeria japonica transition wood. Abstract of the 56th Annual Meeting of the Japan Wood Research Society, Akita, Japan, p 70
Yoshida K, Nishiguchi M, Futamura N, Nanjo T (2006) Expressed sequence tags fromCryptomeria japonica sapwood during the drying process. Tree Physiol 27:1–9
Author information
Authors and Affiliations
Institute of Sustainability Science, Kyoto University, Uji, Kyoto, 611-0011, Japan
Shiro Suzuki & Toshiaki Umezawa
Research Institute for Sustainable Humanosphere, Kyoto University, Uji, Kyoto, 611-0011, Japan
Toshiaki Umezawa
- Shiro Suzuki
You can also search for this author inPubMed Google Scholar
- Toshiaki Umezawa
You can also search for this author inPubMed Google Scholar
Corresponding author
Correspondence toToshiaki Umezawa.
About this article
Cite this article
Suzuki, S., Umezawa, T. Biosynthesis of lignans and norlignans.J Wood Sci53, 273–284 (2007). https://doi.org/10.1007/s10086-007-0892-x
Received:
Accepted:
Published:
Issue Date:
Share this article
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative