4
22
L. Palacio et al. / Process Biochemistry 46 (2011) 418–422
larreatricins, 8-epilarreatricins, 3,3-didemethoxyverrucosins and meso-3,3-
didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence
for regiospecific control of coupling. Org Biomol Chem 2003;1:2307–13.
10] Davicino R, Mattar A, Casali Y, Porporatto C, Correa SG, Micalizzi B. In
vivo immunomodulatory effects of aqueous extracts of Larrea divaricata Cav.
Immunopharmacol Immunotoxicol 2007;29(3–4):351–66.
11] Craigo J, Callahan M, Huang RC, DeLucia AL. Inhibition of human papillomavirus
type 16 gene expression by nordihydroguaiaretic acid plant lignan derivates.
Antivir Res 2000;47:19–28.
[
[
[
12] Whitman S, Gezginci M, Timmermann BN, Holman TR. Structure–activity
relationship studies of nordihydroguaiaretic acid inhibitors toward soy-
bean, 12-human, and 15-human lipoxygenase. Med Chem 2002;45:2659–
61.
[
[
13] Konigheim BS, Goleniowski ME, Contigiani MS. Cytotoxicity and antivi-
ral activity of a lignan extracted from Larrea divaricata. Drug Design Rev
2005;2(1):81–3.
14] Bongiovanni G, Cantero J, Eynard A, Goleniowski M. Organic extracts of Lar-
rea divaricata Cav. induced apoptosis on tumoral MCF7 cells with a higher
cytotoxicity than nordihydroguaiaretic acid or Paclitaxel. J Exp Ther Oncol
2008;7(1):1–7.
[
[
15] Chen Q. Nordihydroguaiaretic acid analogues: their chemical synthesis and
biological activities. Curr Top Med Chem 2009;9:1636–59.
16] Chattopadhyay S, Srivastava AK, Bhojwani SS, Bisaria VS. Production of
podophyllotoxin by plant cell cultures of Podophyllum hexandrum in bioreactor.
J Biosci Bioeng 2002;93(2):215–20.
Fig. 4. Relationship between l-phenylalanine concentrations and the bioconversion
percentage of NDGA, p-coumaric acid and sinapyl alcohol after treating L. divaricata
cell cultures.
[
[
[
17] Uden van W, Pras N, Malingre TM. The accumulation of podophyllotoxin-
-d-glucoside by cell suspension cultures derived from the conifer Callitris
drummondii. Plant Cell Rep 1990;9:257–60.
18] Fürden van B, Humburg A, Fuss E. Influence of methyl jasmonate on podophyl-
lotoxin and 6-methoxypodophyllotoxin accumulation in Linum album cell
suspension cultures. Plant Cell Rep 2005;24(5):312–7.
19] Federolf K, Alfermann AW, Fuss E. 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
2007;68(10):1397–406.
20] Berim A, Spring O, Conrad J, Maitrejean M, Boland W, Petersen M. Enhancement
of lignan biosynthesis in suspension cultures of Linum nodiflorum by coronalon,
indanoyl-isoleucine and methyl jasmonate. Planta 2005;222:769–76.
3
.3. Bioconversion
Transformation of l-phenylalanine into p-coumaric acid, sinapyl
alcohol and NDGA was observed in cell suspension cultures of L.
divaricata. The concentration of 0.5 mM l-phenylalanine was the
most effective on the biotransformation into NDGA, resulting in the
highest level of bioconversion (Fig. 4). There was a positive relation
between the percentage of bioconversion into p-coumaric acid and
the increase in concentration of l-phenylalanine, with the optimal
substrate concentration tested being 3 mM. In contrast, the per-
centage of bioconversion into sinapyl alcohol decreased with the
increase of l-phenylalanine concentrations.
[
[21] Schmitt J, Petersen M. Influence of methyl jasmonate and coniferyl alcohol on
pinoresinol and matairesinol accumulation in a Forsythia × intermedia suspen-
sion culture. Plant Cell Rep 2002;20:885–9.
[
22] Mohagheghzadeh A, Schmidt TJ, Alfermann AW. Arylnaphthalene lignans from
in vitro cultures of Linum austriacum. J Nat Prod 2002;65:69–71.
[
23] Caretto S, Bray Speth E, Fachechi C, Gala R, Zacheo G, Giovinazzo G. Enhance-
ment of vitamin E production in sunflower cell cultures. Plant Cell Rep
Acknowledgements
2
004;23(3):174–9.
The authors thank the Consejo Nacional de Investigaciones Cien-
tíficas y Técnicas (CONICET), Project Grant PIP 02967/2004-2007
and Ministerio de Ciencia y Tecnología, Córdoba, Argentina, Project
Grant No. 757/2004-2008, for funding this work. This study was
carried out as part of a doctoral thesis at the “Facultad de Ciencias
Exactas, Físicas y Naturales, Universidad Nacional de Córdoba”.
[24] Lee M-H, Cheng J-J, Lin C-Y, Chen Y-J, Lu M-K. Precursor-feeding strategy for the
production of solanine, solanidine and solasodine by a cell culture of Solanum
lyratum. Process Biochem 2007;42(5):899–903.
25] Smetanska I. Production of secondary metabolites using plant cell cultures. Adv
Biochem Eng Biotechnol 2008;111:187–228.
[26] Cabrera AL. Regiones Fitogeográficas Argentinas. In: Kugler WF, editor. Enciclo-
pedia Argentina de Agricultura y Jardinería. Bs As, Argentina: ACME SA; 1994.
p. 1–85.
[
[
[
[
[
[
[
[
[
27] Palacio L, Bongiovanni G, Luchino N, Goleniowski ME. Development of an
References
in vitro culture of Larrea divaricata for biomass production. Mol Med Chem
2
006;10:14–6.
28] Murashige T, Skoog F.
bioassays with tobacco tissue cultures. Physiol Plant 1962;15:473–
7.
A
revised medium for rapid growth and
[
[
1] Hieronymus G. Plantae Diaphoricae Florae Argentinae. Bs As, Argentina: Kraft;
882. p. 404.
2] Timmermann BN. Larrea: potential uses. In: Campos Lopez E, Mabry TJ, Fernan-
dez Tavizon S, editors. Larrea. Coah, Saltillo, Mexico: Centro de Investigación
en Química Aplicada; 1979. p. 237–45.
1
9
29] Duncan RD, Widholm JM. Measurements of viability suitable for plant tissue
cultures. In: Pollard JW, Walker JM, editors. Methods in molecular biology.
Totowa: The Humana Press; 1990. p. 29–37.
30] Edhahiro J-I, Nakamura M, Seki M, Furusaki S. Enhanced accumulation of antho-
cyanin in cultured strawberry cells by repetitive feeding of l-phenylalanine into
the medium. J Biosci Bioeng 2005;99(1):43–7.
31] Gao L, Hu X, Xu Z, Xi Y, Shao Y, Chen H, Li Z. Increased flavonoids production
in suspension culture of Saussurea medusa cells by the addition of precursors.
High Technol Lett 2007;17(4):418–23.
32] Luo J, He G-Y. Optimization of elicitors and precursors for paclitaxel production
in cell suspension culture of Taxus chinensis in the presence of nutrient feeding.
Process Biochem 2004;39:1073–9.
33] Cho M-H, Moinuddin SGA, Helms GL, Hishiyama S, Eichinger D, Davin LB, Lewis
NG. (+)-Larreatricin hydroxylase, an enantio-specific polyphenol oxidase from
the creosote bush (Larrea tridentata). Proc Natl Acad Sci 2003;100(19):10641–6.
34] Vassaõ DG, Kim S-J, Milhollan JK, Eichinger D, Davin LB, Laurence B, Lewis LB. A
pinoresinol–lariciresinol reductase homologue from the creosote bush (Larrea
tridentata) catalyzes the efficient in vitro conversion of p-coumaryl/coniferyl
alcohol esters into the allylphenols chavicol/eugenol, but not the propenylphe-
nols p-anol/isoeugenol. Arch Biochem Biophys 2007;465:209–18.
[
[
3] Ratera MO, Ratera EL. Plantas de la Flora Argentina empleadas en la medicina
popular. Bs As, Argentina: Hemisferio Sur; 1980. p. 1–105.
4] Goleniowski M, Bongiovanni GA, Palacio L, Eynard AR, Cantero JJ. Medici-
nal plants from the “Sierra de Comechingones”, Argentina. J Ethnopharmacol
2
006;107:324–41.
[
[
[
5] Vilela A, Bolkovic ML, Carmanchahi P, Cony M, de Lamo D, Wassner D. Past,
present and potential uses of native flora and wildlife of the Monte Desert. J
Arid Environ 2009;73:238–43.
6] Barboza GE, Cantero JJ, Nu n˜ ez CO, Ariza Espinar L. Flora medicinal de la Provin-
cia de Córdoba (Argentina). Córdoba, Argentina: Museo de Botánica, UNC; 2006.
p. 1168–1171.
7] Davin LB, Lewis NG. Dirigent proteins and dirigent sites explain the mystery of
specificity of radical precursor coupling in lignan and lignin biosynthesis. Plant
Physiol 2000;123:453–62.
[
[
8] Petersen M, Alfermann AW. The production of cytotoxic lignans by plant cell
cultures. Appl Microbiol Biotechnol 2001;55(2):135–42.
9] Moinuddin SGA, Hishiyama S, Cho M-H, Davin LB, Lewis NG. Syn-
thesis and chiral HPLC analysis of the dibenzyltetrahydrofuran lignans,