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Essences in metabolic engineering of lignan biosynthesis.

Satake H, Koyama T, Bahabadi SE, Matsumoto E, Ono E, Murata J - Metabolites (2015)

Bottom Line: Accordingly, the development of new procedures for lignan production is of keen interest.Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted.This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

View Article: PubMed Central - PubMed

Affiliation: Bioorganic Research Institute, Suntory Foundation for Life Sciences, Osaka 618-8503, Japan. satake@sunbor.or.jp.

ABSTRACT
Lignans are structurally and functionally diverse phytochemicals biosynthesized in diverse plant species and have received wide attentions as leading compounds of novel drugs for tumor treatment and healthy diets to reduce of the risks of lifestyle-related non-communicable diseases. However, the lineage-specific distribution and the low-amount of production in natural plants, some of which are endangered species, hinder the efficient and stable production of beneficial lignans. Accordingly, the development of new procedures for lignan production is of keen interest. Recent marked advances in the molecular and functional characterization of lignan biosynthetic enzymes and endogenous and exogenous factors for lignan biosynthesis have suggested new methods for the metabolic engineering of lignan biosynthesis cascades leading to the efficient, sustainable, and stable lignan production in plants, including plant cell/organ cultures. Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted. This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

No MeSH data available.


Related in: MedlinePlus

Metabolic Engineering of Forsythia Suspension Cell Cultures. The Transgenic Forsythia Suspension Cell Culture, CPi-Fk cells, Acquired the Ability to Produce Sesamin by Stable Transfection of PLR-RNAi and the SesamumCYP81Q1 Gene.
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metabolites-05-00270-f003: Metabolic Engineering of Forsythia Suspension Cell Cultures. The Transgenic Forsythia Suspension Cell Culture, CPi-Fk cells, Acquired the Ability to Produce Sesamin by Stable Transfection of PLR-RNAi and the SesamumCYP81Q1 Gene.

Mentions: Forsythia is a perennial plant commonly known as the golden bell flower, and is used for a variety of Chinese medicines and health diets [1,2,5,7,12,55]. As shown in Figure 2, Forsythia biosynthesizes pinoresinol, phillygenin, secoisolariciresinol, matairesinol, and arctigenin, with >90% of pinoresinol, > 80% of matairesiol, and 40%–80% of arctigenin accumulated in glucosylated forms [1,2,63,64,83]. Identification of these lignans and the relevant biosynthetic enzymes suggests the potential of Forsythia as a platform for lignan production. Although efficient methods for the generation of transgenic Forsythia species have not yet been established [84], the metabolic engineering of Forsythia culture cells was originally reported. Forsythia suspension cells stably transfected with a PLR-RNA interference (RNAi) sequence (PLR-RNAi) showed complete loss of matairesinol and an approximately 20-fold increase in total pinoresinol (pinoresinol aglycone and glucoside), compared with the wildtype cells [63]. Furthermore, Forsythia transgenic cells, CPi-Fk, which are stably double-transfected with PLR-RNAi and the sesamin-producing enzyme, CYP81Q1 (Figure 2), produced sesamin (0.01 mg/g dry weight of the cell [DW]) (Figure 3), although sesamin is not biosynthesized in native Forsythia [63]. This is the first success in lignan metabolic engineering leading to an exogenous lignan using transgenic plant cells. In addition, the RNAi-based suppression of UGT71A18 (encoding a pinoresinol-glucosylating enzyme) may lead to the dramatic improvement of sesamin production in CPi-Fk cells, given that pinoresinol glucoside cannot be utilized by CYP81Q1 as a substrate [75], and 90% of pinoresinol is glucosylated in Forsythia cells [1,2,63,64,83]. Thus, the Forsythia cell culture system is an efficient and promising platform for producing both endogenous and exogenous lignans by transgenic metabolic engineering.


Essences in metabolic engineering of lignan biosynthesis.

Satake H, Koyama T, Bahabadi SE, Matsumoto E, Ono E, Murata J - Metabolites (2015)

Metabolic Engineering of Forsythia Suspension Cell Cultures. The Transgenic Forsythia Suspension Cell Culture, CPi-Fk cells, Acquired the Ability to Produce Sesamin by Stable Transfection of PLR-RNAi and the SesamumCYP81Q1 Gene.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495373&req=5

metabolites-05-00270-f003: Metabolic Engineering of Forsythia Suspension Cell Cultures. The Transgenic Forsythia Suspension Cell Culture, CPi-Fk cells, Acquired the Ability to Produce Sesamin by Stable Transfection of PLR-RNAi and the SesamumCYP81Q1 Gene.
Mentions: Forsythia is a perennial plant commonly known as the golden bell flower, and is used for a variety of Chinese medicines and health diets [1,2,5,7,12,55]. As shown in Figure 2, Forsythia biosynthesizes pinoresinol, phillygenin, secoisolariciresinol, matairesinol, and arctigenin, with >90% of pinoresinol, > 80% of matairesiol, and 40%–80% of arctigenin accumulated in glucosylated forms [1,2,63,64,83]. Identification of these lignans and the relevant biosynthetic enzymes suggests the potential of Forsythia as a platform for lignan production. Although efficient methods for the generation of transgenic Forsythia species have not yet been established [84], the metabolic engineering of Forsythia culture cells was originally reported. Forsythia suspension cells stably transfected with a PLR-RNA interference (RNAi) sequence (PLR-RNAi) showed complete loss of matairesinol and an approximately 20-fold increase in total pinoresinol (pinoresinol aglycone and glucoside), compared with the wildtype cells [63]. Furthermore, Forsythia transgenic cells, CPi-Fk, which are stably double-transfected with PLR-RNAi and the sesamin-producing enzyme, CYP81Q1 (Figure 2), produced sesamin (0.01 mg/g dry weight of the cell [DW]) (Figure 3), although sesamin is not biosynthesized in native Forsythia [63]. This is the first success in lignan metabolic engineering leading to an exogenous lignan using transgenic plant cells. In addition, the RNAi-based suppression of UGT71A18 (encoding a pinoresinol-glucosylating enzyme) may lead to the dramatic improvement of sesamin production in CPi-Fk cells, given that pinoresinol glucoside cannot be utilized by CYP81Q1 as a substrate [75], and 90% of pinoresinol is glucosylated in Forsythia cells [1,2,63,64,83]. Thus, the Forsythia cell culture system is an efficient and promising platform for producing both endogenous and exogenous lignans by transgenic metabolic engineering.

Bottom Line: Accordingly, the development of new procedures for lignan production is of keen interest.Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted.This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

View Article: PubMed Central - PubMed

Affiliation: Bioorganic Research Institute, Suntory Foundation for Life Sciences, Osaka 618-8503, Japan. satake@sunbor.or.jp.

ABSTRACT
Lignans are structurally and functionally diverse phytochemicals biosynthesized in diverse plant species and have received wide attentions as leading compounds of novel drugs for tumor treatment and healthy diets to reduce of the risks of lifestyle-related non-communicable diseases. However, the lineage-specific distribution and the low-amount of production in natural plants, some of which are endangered species, hinder the efficient and stable production of beneficial lignans. Accordingly, the development of new procedures for lignan production is of keen interest. Recent marked advances in the molecular and functional characterization of lignan biosynthetic enzymes and endogenous and exogenous factors for lignan biosynthesis have suggested new methods for the metabolic engineering of lignan biosynthesis cascades leading to the efficient, sustainable, and stable lignan production in plants, including plant cell/organ cultures. Optimization of light conditions, utilization of a wide range of elicitor treatments, and construction of transiently gene-transfected or transgenic lignan-biosynthesizing plants are mainly being attempted. This review will present the basic and latest knowledge regarding metabolic engineering of lignans based on their biosynthetic pathways and biological activities, and the perspectives in lignan production via metabolic engineering.

No MeSH data available.


Related in: MedlinePlus