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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

Chemical Structures of Typical Lignans in (A) Dietary and Medicinal Sources and (B) Synthetic Podophyllotoxin Derivatives.
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metabolites-05-00270-f001: Chemical Structures of Typical Lignans in (A) Dietary and Medicinal Sources and (B) Synthetic Podophyllotoxin Derivatives.

Mentions: Dietary supplements and drug compounds are largely derived from specialized metabolites, previously called secondary metabolites of plants, including alkaloids, flavonoids, isoflavonoids, and lignans. As depicted in Figure 1A, lignans are naturally occurring phenylpropanoid dimers (C6-C3 unit; e.g., coniferyl alcohol), in which the phenylpropane units are linked by the central carbons of the side chains. These specialized metabolites are classified into eight groups based on their structural patterns, including their carbon skeletons; the way in which oxygen is incorporated into the skeletons; and the cyclization pattern: furofuran, furan, dibenzylbutane, dibenzylbutyrolactone, aryltetralin, arylnaphthalene, dibenzocyclooctadiene, and dibenzylbutyrolactol [1,2]. Unfortunately, the amounts of lignans and their precursor molecules in model plants such as Arabidopsis thaliana and Nicotiana tabacum are quite low. Moreover, plant sources of lignans are frequently limited because of the high cost of plant hunting and collection, poor cultivation systems, long growth phase, and the low lignan content [1,2,3,4,5,6,7,8,9,10,11,12]. For instance, sesamin, a multifunctional sesame seed lignan, is extracted from sesame seed oil, the most abundant source of this compound. Nevertheless, sesamin at most constitutes 0.4%–0.6% (w/w) of sesame seed oil. Moreover, sesame seeds are cultivated only once per year, limiting the ability to obtain large amounts of this compound. Likewise, podophyllotoxin (PTOX), a lignan that is a precursor of semi-synthetic anti-tumor drugs, is isolated from the roots and rhizomes of Podophyllum hexandrum, which is distributed in very limited regions, and is now endangered due to overharvesting and environmental disruption [13]. In addition, the complicated chemical structures of PTOX and the related compounds (Figure 1A) make stereoselective organic synthesis impractical and costly for producing large supplies of these compounds and the resulting high cost [1,2,3,4,5,6,7,8,9,10,11,12]. These drawbacks indicate the requirement for efficient, stable and sustainable production systems for producing lignans.


Essences in metabolic engineering of lignan biosynthesis.

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

Chemical Structures of Typical Lignans in (A) Dietary and Medicinal Sources and (B) Synthetic Podophyllotoxin Derivatives.
© Copyright Policy
Related In: Results  -  Collection

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

metabolites-05-00270-f001: Chemical Structures of Typical Lignans in (A) Dietary and Medicinal Sources and (B) Synthetic Podophyllotoxin Derivatives.
Mentions: Dietary supplements and drug compounds are largely derived from specialized metabolites, previously called secondary metabolites of plants, including alkaloids, flavonoids, isoflavonoids, and lignans. As depicted in Figure 1A, lignans are naturally occurring phenylpropanoid dimers (C6-C3 unit; e.g., coniferyl alcohol), in which the phenylpropane units are linked by the central carbons of the side chains. These specialized metabolites are classified into eight groups based on their structural patterns, including their carbon skeletons; the way in which oxygen is incorporated into the skeletons; and the cyclization pattern: furofuran, furan, dibenzylbutane, dibenzylbutyrolactone, aryltetralin, arylnaphthalene, dibenzocyclooctadiene, and dibenzylbutyrolactol [1,2]. Unfortunately, the amounts of lignans and their precursor molecules in model plants such as Arabidopsis thaliana and Nicotiana tabacum are quite low. Moreover, plant sources of lignans are frequently limited because of the high cost of plant hunting and collection, poor cultivation systems, long growth phase, and the low lignan content [1,2,3,4,5,6,7,8,9,10,11,12]. For instance, sesamin, a multifunctional sesame seed lignan, is extracted from sesame seed oil, the most abundant source of this compound. Nevertheless, sesamin at most constitutes 0.4%–0.6% (w/w) of sesame seed oil. Moreover, sesame seeds are cultivated only once per year, limiting the ability to obtain large amounts of this compound. Likewise, podophyllotoxin (PTOX), a lignan that is a precursor of semi-synthetic anti-tumor drugs, is isolated from the roots and rhizomes of Podophyllum hexandrum, which is distributed in very limited regions, and is now endangered due to overharvesting and environmental disruption [13]. In addition, the complicated chemical structures of PTOX and the related compounds (Figure 1A) make stereoselective organic synthesis impractical and costly for producing large supplies of these compounds and the resulting high cost [1,2,3,4,5,6,7,8,9,10,11,12]. These drawbacks indicate the requirement for efficient, stable and sustainable production systems for producing lignans.

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