Phytochemistry Reviews

, Volume 13, Issue 4, pp 893–913 | Cite as

Biotechnological approaches for producing aryltetralin lignans from Linum species

  • S. Malik
  • O. Bíba
  • J. Grúz
  • R. R. J. Arroo
  • M. Strnad


The genus Linum includes more than 230 globally distributed species, which have attracted great interest as they grow rapidly and are already sources of commercially important products, e.g. flax and linseed oil. Furthermore, they contain lignans such as podophyllotoxin (PTOX), deoxypodophyllotoxin (a precursor of both PTOX and 6-methoxypodophyllotoxin, the latter via β-peltatin, and β-peltatin-A-methyl ether) and various derivatives. Lignans are natural compounds derived from two 8,8′-linked C6C3 (propylbenzene) units. PTOX is an aryltetralin-lignan with strong cytotoxic and antiviral activities. Thus, it is used as a starting material for producing various semisynthetic derivatives that are widely used in chemotherapy, such as etoposide, teniposide and etopophos. It is currently produced largely from Podophyllum hexandrum and P. peltatum, slow-growing endangered species of the Berberidaceae. Hence, the possibility of producing it from Linum, especially members of section Syllinum under either in vitro or ex vitro conditions is highly attractive. This review summarizes related research, focusing on in vitro production of aryltetralin lignans from various Linum species and possible biotechnological strategies to improve their production. The key pathways, enzymes and genes involved are highlighted and future challenges that must be met to allow viable, large-scale production of this anticancer drug lead are discussed.


6-Methoxypodophyllotoxin Anticancer drugs In vitro cultures Lignans Podophyllotoxin Medicinal plants 





Dry weight








Methyl jasmonate


Salicylic acid



This work was further supported by the Centre of the Region Haná for Biotechnological and Agricultural Research (ED0007/01/01) and the Czech Grant Agency (Grant No. 14-19590S).


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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • S. Malik
    • 1
  • O. Bíba
    • 1
    • 2
  • J. Grúz
    • 1
    • 2
  • R. R. J. Arroo
    • 3
  • M. Strnad
    • 1
    • 2
  1. 1.Faculty of Science, Centre of the Region Haná for Biotechnological and Agricultural ResearchPalacký UniversityOlomoucCzech Republic
  2. 2.Laboratory of Growth Regulators, Institute of Experimental Botany AS CRPalacký UniversityOlomoucCzech Republic
  3. 3.Leicester School of PharmacyDe Montfort UniversityLeicesterUK

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