Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition.

Yun, Dae‐Jin; Hashimoto, Takashi; Yamada, Yasuyuki

doi:10.1073/pnas.89.24.11799

Cited by 272 publications

(89 citation statements)

References 27 publications

(27 reference statements)

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“…An even smaller number of pathways have been manipulated using molecular, genetic, or biochemical tools. Examples of such pathways include flavonoid biosynthesis (Van der Krol et al, 1990), lignins (Guo et al, 2001, carotenoids (Rö mer et al, 2000;Ye et al, 2000), fatty acids (Kinney, 1998), and some secondary metabolic pathways (Yun and Hashimoto, 1992;Nessler, 1994). Different approaches have been used to understand metabolic processes in plants.…”

Section: Discussionmentioning

confidence: 99%

Expression of a Heterologous S-Adenosylmethionine Decarboxylase cDNA in Plants Demonstrates That Changes inS-Adenosyl-l-Methionine Decarboxylase Activity Determine Levels of the Higher Polyamines Spermidine and Spermine

et al. 2002

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We posed the question of whether steady-state levels of the higher polyamines spermidine and spermine in plants can be influenced by overexpression of a heterologous cDNA involved in the later steps of the pathway, in the absence of any further manipulation of the two synthases that are also involved in their biosynthesis. Transgenic rice (Oryza sativa) plants engineered with the heterologous Datura stramonium S-adenosylmethionine decarboxylase (samdc) cDNA exhibited accumulation of the transgene steady-state mRNA. Transgene expression did not affect expression of the orthologous samdc gene. Significant increases in SAMDC activity translated to a direct increase in the level of spermidine, but not spermine, in leaves. Seeds recovered from a number of plants exhibited significant increases in spermidine and spermine levels. We demonstrate that overexpression of the D. stramonium samdc cDNA in transgenic rice is sufficient for accumulation of spermidine in leaves and spermidine and spermine in seeds. These findings suggest that increases in enzyme activity in one of the two components of the later parts of the pathway leading to the higher polyamines is sufficient to alter their levels mostly in seeds and, to some extent, in vegetative tissue such as leaves. Implications of our results on the design of rational approaches for the modulation of the polyamine pathway in plants are discussed in the general framework of metabolic pathway engineering.Relatively few pathways have been elucidated molecularly and biochemically in plants, and an even smaller number are amenable to modulation by molecular approaches. This is because of the complex nature of metabolic networks that are often regulated at different levels, spatially and temporally. In our ongoing efforts to implement rational molecular approaches to modulate plant metabolism, we chose the polyamine pathway as a model to unravel those key factors that still present bottlenecks in pathway engineering. The polyamine pathway is ubiquitous in living organisms (Bagni, 1989). It is a relatively short pathway in terms of the number of enzymes involved, however, it is rather complex because of its impact on crucial physiological, developmental, and regulatory processes in which polyamines are implicated (Malmberg et al., 1998). All enzymes involved in the pathway have been characterized, and corresponding genes/cDNAs have been cloned from different sources (Kumar and Minocha, 1998). As a result, the pathway represents an ideal model to test hypotheses and to answer fundamental biological questions in pathway manipulation using transgenesis.The polyamine pathway comprises an anabolic phase leading to the elaboration of spermidine and spermine from putrescine. Orn decarboxylase (ODC; EC 4.1.1.19) catalyzes the removal of the carboxyl group from Orn to yield putrescine, whereas S-adenosyl-l-Met (SAM) decarboxylase (SAMDC; EC 4.1.1.50), introduces SAM into the pathway, which is then used in its decarboxylated form (dcSAM) as an aminopropyl donor in the conversion of putre...

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Section: Discussionmentioning

confidence: 99%

Expression of a Heterologous S-Adenosylmethionine Decarboxylase cDNA in Plants Demonstrates That Changes inS-Adenosyl-l-Methionine Decarboxylase Activity Determine Levels of the Higher Polyamines Spermidine and Spermine

et al. 2002

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“…Such genetically engineered hairy roots should be useful for enhancing scopolamine productivity in in vitro root culture systems. At the same time, Yun et al (1992) also introduced h6h into A. belladonna by use of Agrobacterium tumefaciens. In the primary transformation and its selfed progeny that inherited the transgene, the alkaloid content of the leaf and stem was almost exclusively scopolamine.…”

Section: Engineering Single Stepmentioning

confidence: 99%

Metabolic Engineering of Tropane Alkaloid Biosynthesis in Plants

Zhang

Kai

Lü

et al. 2005

J Integrative Plant Biology

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Over the past decade, the evolving commercial importance of so-called plant secondary metabolites has resulted in a great interest in secondary metabolism and, particularly, in the possibilities to enhance the yield of fine metabolites by means of genetic engineering. Plant alkaloids, which constitute one of the largest groups of natural products, provide many pharmacologically active compounds. Several genes in the tropane alkaloids biosynthesis pathways have been cloned, making the metabolic engineering of these alkaloids possible. The content of the target chemical scopolamine could be significantly increased by various approaches, such as introducing genes encoding the key biosynthetic enzymes or genes encoding regulatory proteins to overcome the specific rate-limiting steps. In addition, antisense genes have been used to block competitive pathways. These investigations have opened up new, promising perspectives for increased production in plants or plant cell culture. Recent achievements have been made in the metabolic engineering of plant tropane alkaloids and some new powerful strategies are reviewed in the present paper.

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“…If the same PMT gene in D. metel was overexpressed, the TA content was significantly increased by almost four times that of the control [140]. H6H has a high catalytic efficiency for converting hyoscyamine (4) to scopolamine (3) [141]. The overexpression of the H6H gene resulted in an increase in the biosynthesis of scopolamine (3) in the transformed TA producing plant, A. belladonna.…”

Section: Metabolic Engineeringmentioning

confidence: 95%

“…Another successful use of H6H was in transgenic Hyoscyamus muticus hairy root cultures, where scopolamine (3) levels increased to over 100 times that of the controls [142]. Furthermore, overexpression of H6H in transgenic A. belladonna plants resulted in the leaf and stem alkaloid contents to be exclusively scopolamine (3) [141].…”

Section: Metabolic Engineeringmentioning

confidence: 99%

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

et al. 2016

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Abstract:The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring to their core ring structures. Throughout much of human history, humans have cultivated tropane-and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. In addition, modern approaches to producing some pharmaceutically important tropanes via metabolic engineering endeavors are discussed.

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Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition.

Cited by 272 publications

References 27 publications

Expression of a Heterologous S-Adenosylmethionine Decarboxylase cDNA in Plants Demonstrates That Changes inS-Adenosyl-l-Methionine Decarboxylase Activity Determine Levels of the Higher Polyamines Spermidine and Spermine

Expression of a Heterologous S-Adenosylmethionine Decarboxylase cDNA in Plants Demonstrates That Changes inS-Adenosyl-l-Methionine Decarboxylase Activity Determine Levels of the Higher Polyamines Spermidine and Spermine

Metabolic Engineering of Tropane Alkaloid Biosynthesis in Plants

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

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