Linum album

In addition to podophyllotoxin itself, closely related compounds, such as 5-methoxypodophyllotoxin (3.89), can be used as a precursor for anti-cancer drugs. Linum species (flax, linseed) can produce podophyllotoxin or substituted podophyllotoxins in tissue culture with yields of up to 0.35% of dry weight. The biosynthesis of 5-methoxypodophyllotoxin in Linum flavum was investigated by Xia et al. (2000), whereas Seidel et al. (2002) investigated podophyllotoxin (3.86) production in cell cultures of Linum album. 

Synthesis of podophyllotoxin (3.86) in cell culture of Linum album results in yields comparable to those of the most efficient tissue cultures of Podophyllum hexandrum. In order to further improve L. album cultures, Seidel et al. (2002) investigated the biosynthesis of podophyllotoxin (3.86). They fed a number of labeled compounds that to L. album cell cultures to identify which of these compounds could be used as precursors to podophyllotoxin. They determined that the substitution pattern on the benzene ring is critical. The substitution has to be either 3-methoxy, 4-hydroxy, as in ferulic acid (3.33), or, alternatively, 3,4-methylenedioxycinnamic acid (3.90) can serve as precursor. The precursor of podophyllotoxin in L. album appears to be deoxypodophyllotoxin (3.83), based on the higher level of isotope incorporation in the latter compound. This means that 7-hydroxymatairesinol, the precursors of 5-methoxypodophyllotoxin in L. flavum (Xia et al., 2000), is not a precursor of podophyllotoxin in L. album. 

Federolf, K., Alfermann, A.W. and Fuss, E. (2007) Aryltetralin-lignan formation in two different cell suspension cultures of Linum album Deoxypodophyllotoxin 6-hydroxylase, a key enzyme for the formation of 6-methoxypodophyllotoxin. Phytochemistry, 68,1397-A06. 

Henges, A. (1999) Biosynthese und Kompartimentierung von Lignanen in Zell-kulturen von Linum album. PhD Thesis, Heinrich-Heine-Universitat Diisseldorf, Germany. 

Smollny, T., Wichers, H., Kalenberg, S., Shahsavari, A., Petersen, M. and Alfermarm, A.W. (1998) Accumulation of podophyllotoxin and related lignans in cell suspension cultures of Linum album. Phytochemistry, 48, 975-79. 

Seidel V, et al. Biosynthesis of podophyllotoxin in Linum album cell cultures. Planta 2002 215 1031-1039. 

N. et al. (2010) Enhanced production of podophyllotoxins by co-culture of transformed Linum album cells with plant growth-promoting fungi. Pure Appl Chem., 82, 227 - 241. 

Fig. 12.7 Reactions catalyzed by pinoresinol/lariciresinol reductases from Forsythia intermedia (PLR-Fil) [34], Thujaplicata (PLR-Tpl and PLR-Tp2) [37], Liram album (PLR-Lal) [41], Linum perenne (PLR-Lpl) [42], and Linum usitatissimum (PLR-Lul) [41] and pinoresinol reductases from Arabidopsis thaliana (AtPrRl and AtPrR2) [55]...

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