Abstract
Lignans are a widely distributed class of natural products, whose functions and distribution suggest that they are one of the earliest forms of defense to have evolved in vascular plants; some, such as podophyllotoxin and enterodiol, have important roles in cancer chemotherapy and prevention, respectively. Entry into lignan enzymology has been gained by the ~3000- fold purification of two isoforms of (+)-pinoresinol/(+)-lariciresinol reductase, a pivotal branchpoint enzyme in lignan biosynthesis. Both have comparable (~34.9 kDa) molecular mass and kinetic (V(max)/K(m)) properties and catalyze sequential, NADPH-dependent, stereospecific, hydride transfers where the incoming hydride takes up the pro-R position. The gene encoding (+)-pinoresinol/(+)-lariciresinol reductase has been cloned and the recombinant protein heterologously expressed as a functional β- galactosidase fusion protein. Its amino acid sequence reveals a strong homology to isoflavone reductase, a key branchpoint enzyme in isoflavonoid metabolism and primarily found in the Fabaceae (angiosperms). This is of great evolutionary significance since both lignans and isoflavonoids have comparable plant defense properties, as well as similar roles as phytoestrogens. Given that lignans are widespread from primitive plants onwards, whereas the isoflavone reductase-derived isoflavonoids are mainly restricted to the Fabaceae, it is tempting to speculate that this branch of the isoflavonoid pathway arose via evolutionary divergence from that giving the lignans.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 29473-29482 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 271 |
| Issue number | 46 |
| DOIs | |
| State | Published - 1996 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
(+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia : Protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase. / Dinkova-Kostova, Albena T.; Gang, David R.; Davin, Laurence B.; Bedgar, Diana L.; Chu, Alex; Lewis, Norman G.
In: Journal of Biological Chemistry, Vol. 271, No. 46, 1996, p. 29473-29482.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia
T2 - Protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase
AU - Dinkova-Kostova, Albena T.
AU - Gang, David R.
AU - Davin, Laurence B.
AU - Bedgar, Diana L.
AU - Chu, Alex
AU - Lewis, Norman G.
PY - 1996
Y1 - 1996
N2 - Lignans are a widely distributed class of natural products, whose functions and distribution suggest that they are one of the earliest forms of defense to have evolved in vascular plants; some, such as podophyllotoxin and enterodiol, have important roles in cancer chemotherapy and prevention, respectively. Entry into lignan enzymology has been gained by the ~3000- fold purification of two isoforms of (+)-pinoresinol/(+)-lariciresinol reductase, a pivotal branchpoint enzyme in lignan biosynthesis. Both have comparable (~34.9 kDa) molecular mass and kinetic (V(max)/K(m)) properties and catalyze sequential, NADPH-dependent, stereospecific, hydride transfers where the incoming hydride takes up the pro-R position. The gene encoding (+)-pinoresinol/(+)-lariciresinol reductase has been cloned and the recombinant protein heterologously expressed as a functional β- galactosidase fusion protein. Its amino acid sequence reveals a strong homology to isoflavone reductase, a key branchpoint enzyme in isoflavonoid metabolism and primarily found in the Fabaceae (angiosperms). This is of great evolutionary significance since both lignans and isoflavonoids have comparable plant defense properties, as well as similar roles as phytoestrogens. Given that lignans are widespread from primitive plants onwards, whereas the isoflavone reductase-derived isoflavonoids are mainly restricted to the Fabaceae, it is tempting to speculate that this branch of the isoflavonoid pathway arose via evolutionary divergence from that giving the lignans.
AB - Lignans are a widely distributed class of natural products, whose functions and distribution suggest that they are one of the earliest forms of defense to have evolved in vascular plants; some, such as podophyllotoxin and enterodiol, have important roles in cancer chemotherapy and prevention, respectively. Entry into lignan enzymology has been gained by the ~3000- fold purification of two isoforms of (+)-pinoresinol/(+)-lariciresinol reductase, a pivotal branchpoint enzyme in lignan biosynthesis. Both have comparable (~34.9 kDa) molecular mass and kinetic (V(max)/K(m)) properties and catalyze sequential, NADPH-dependent, stereospecific, hydride transfers where the incoming hydride takes up the pro-R position. The gene encoding (+)-pinoresinol/(+)-lariciresinol reductase has been cloned and the recombinant protein heterologously expressed as a functional β- galactosidase fusion protein. Its amino acid sequence reveals a strong homology to isoflavone reductase, a key branchpoint enzyme in isoflavonoid metabolism and primarily found in the Fabaceae (angiosperms). This is of great evolutionary significance since both lignans and isoflavonoids have comparable plant defense properties, as well as similar roles as phytoestrogens. Given that lignans are widespread from primitive plants onwards, whereas the isoflavone reductase-derived isoflavonoids are mainly restricted to the Fabaceae, it is tempting to speculate that this branch of the isoflavonoid pathway arose via evolutionary divergence from that giving the lignans.
UR - http://www.scopus.com/inward/record.url?scp=0029825803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029825803&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.46.29473
DO - 10.1074/jbc.271.46.29473
M3 - Article
C2 - 8910615
AN - SCOPUS:0029825803
VL - 271
SP - 29473
EP - 29482
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -