Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed.
Application of stable and radioisotope precursor/tracer experiments resulted in the identification of various phenylpropanoid, monolignol, and lignan metabolites involved in the biosynthesis of the cancer chemopreventive secoisolariciresinol diglucoside (SDG; 1)-containing ester-linked "polymer(s)" in flax (Linum usitatissimum) seed. Individual analysis of size-segregated flax seed capsules at five early stages of their development provided a metabolic profile of intermediates leading to "biopolymer" biosynthesis. The use of (1)H and (13)C NMR and HRMS analyses resulted in the identification of 6a-HMG (hydroxymethyl glutaryl) SDG (17) and 6a,6a'-di-HMG SDG (18) as the two major components of the ester-linked "biopolymer(s)". Based on metabolic tracer analyses and relative radioisotopic incorporations throughout each of these five stages of seed development, a biochemical pathway is proposed from phenylalanine to SDG (1), with subsequent mono- and di-substitutions of SDG (1) with HMG CoA. These metabolites then serve as precursors for formation of the SDG-HMG ester-linked oligomers. Results from this study will facilitate future isolation and characterization of the proteins and enzymes involved in biosynthesis of the SDG-HMG ester-linked oligomers in flax seed.
Ford
J D
JD
Institute of Biological Chemistry, Washington State University, Pullman, Washington 99164-6340, USA.
Huang
K S
KS
Wang
H B
HB
Davin
L B
LB
Lewis
N G
NG
D001562:Benzimidazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002072:Butylene Glycols / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D019597:Flax / Q000737:chemistry* / Q000196:embryology; D008401:Gas Chromatography-Mass Spectrometry; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D010666:Phenylpropionates / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012639:Seeds / Q000737:chemistry / Q000196:embryology; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013777:Tetrazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
C442704:6a,6a'-di-hydroxymethylglutarylsecoisolariciresinol diglucoside; C442703:6a-hydroxymethyl glutarylsecoisolariciresinol diglucoside; D001562:Benzimidazoles; D002072:Butylene Glycols; D002250:Carbon Radioisotopes; D005960:Glucosides; D017705:Lignans; D010666:Phenylpropionates; D011108:Polymers; D013777:Tetrazoles; D010649:Phenylalanine; C090142:secoisolariciresinol diglucoside