Recent progress in the metabolic engineering of alkaloids in plant systems

Glenn, Weslee S.; Runguphan, Weerawat; O’Connor, Sarah E.

doi:10.1016/j.copbio.2012.08.003

Cited by 88 publications

(56 citation statements)

References 59 publications

(85 reference statements)

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“…On the other, despite patchy knowledge of biosynthetic networks [79,82], accumulation of valuable metabolites strictly dependent on plant growth conditions and developmental stage, and the persistent shortage of efficient transformation protocols, the demand for antitumor alkaloids, vinblastine and vincristine [83] (Fig. 3), drives a tremendous research effort focused on their producer, C. roseus, dubbed the "model non-model system for alkaloid biosynthesis investigation" [62,84].…”

Section: Monoterpenoid Indole Alkaloids (Mias)mentioning

confidence: 99%

Natural products – modifying metabolite pathways in plants

Staniek

Bouwmeester²,

Fraser

et al. 2013

Biotechnology Journal

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The diversity of plant natural product (PNP) molecular structures is reflected in the variety of biochemical and genetic pathways that lead to their formation and accumulation. Plant secondary metabolites are important commodities, and include fragrances, colorants, and medicines. Increasing the extractable amount of PNP through plant breeding, or more recently by means of metabolic engineering, is a priority. The prerequisite for any attempt at metabolic engineering is a detailed knowledge of the underlying biosynthetic and regulatory pathways in plants. Over the past few decades, an enormous body of information about the biochemistry and genetics of biosynthetic pathways involved in PNPs production has been generated. In this review, we focus on the three large classes of plant secondary metabolites: terpenoids (or isoprenoids), phenylpropanoids, and alkaloids. All three provide excellent examples of the tremendous efforts undertaken to boost our understanding of biosynthetic pathways, resulting in the first successes in plant metabolic engineering. We further consider what essential information is still missing, and how future research directions could help achieve the rational design of plants as chemical factories for high-value products.

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Section: Monoterpenoid Indole Alkaloids (Mias)mentioning

confidence: 99%

Natural products – modifying metabolite pathways in plants

Staniek

Bouwmeester²,

Fraser

et al. 2013

Biotechnology Journal

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“…Overall, it has been concluded that the unique hexacyclic nudicaulin skeleton is the result of the biochemical fusion of an indole moiety with a flavonoid‐like C 6 ‐C 3 ‐C 6 unit of phenylpropanoid/polyketide biogenetic origin. The indole biosynthetic pathway is well established15 and proceeds through anthranilate, N ‐(5‐phosphoribosyl)anthranilate as the substrate for indole‐3‐glycerol phosphate synthase, forming indole‐3‐glycerol phosphate, and, further downstream, indole, l ‐tryptophan, and tryptamine. The principal question of whether or not indole, l ‐tryptophan, or tryptamine could act as the key precursor of the indole part of nudicaulins was not determined by the retro‐biosynthetic study and therefore remained to be answered in this work.…”

Section: Introductionmentioning

confidence: 99%

Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

et al. 2016

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Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid‐indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l‐tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor‐directed incorporation of cyanidin into a new 3′‐hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins.

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“…Similarly, most significant pathways such as photosynthesis and glycolysis/gluconeogenesis (Fig. S16d) also augmented its involvement in regulating primary metabolic pathways as well as synthesis of precursors in upstream of TIA pathway (Aniszewski 2007;Glenn et al 2013). It has also been stated earlier that the initial committed steps in secondary metabolite synthesis are recruited from primary metabolic pathways (Aharoni and Galili 2011;Chu et al 2011).…”

Section: Enrichment Analysis Of Modulesmentioning

confidence: 98%

Computational Analysis of “-omics” Data to Identify Transcription Factors Regulating Secondary Metabolism in Rauvolfia serpentina

Pathania

Acharya

2015

Plant Mol Biol Rep

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Rauvolfia serpentina has been known to produce therapeutically important indole alkaloids used in treatment of various diseases. Despite its medicinal importance, complete understanding of its secondary metabolism is challenging due to complex interplay among various transcription factors (TFs) and genes. However, weighted co-expression analysis of transcriptome along with integration of metabolomics data has proficiency to elucidate topological properties of complex regulatory interactions in secondary metabolism. We aimed to implement an integrative strategy using B-omicsd ata to identify TFs of Bunknown function^and exemplify their role in regulation of valuable metabolites as well as metabolic traits. A total of 69 TFs were identified through significant thresholds and removal of false positives based on cisregulatory motif analysis. Network-biology inspired analysis of co-expression network lead to generation of four statistically significant and biologically robust modules. Similar to known regulatory roles of WRKY and AP2-EREBP TF families in Catharanthus roseus, this study presented them to regulate synthesis of alkaloids in R. serpentina as well.Moreover, TFs in module 4 were observed to be regulating connecting steps between primary and secondary metabolic pathways in the synthesis of terpenoid indole alkaloids. Integration of metabolomics data further highlight the significance of module 1 since it was statistically predicted to be involved in synthesis of specialized metabolites, and associated genes may physically clustered on genome. Importantly, putative TFs in module 1 may modulate the major indole alkaloids synthesis in response to various environmental stimuli. The methodology implemented herein may provide a better reference to identify and explore functions of transcriptional regulators.

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Recent progress in the metabolic engineering of alkaloids in plant systems

Cited by 88 publications

References 59 publications

Natural products – modifying metabolite pathways in plants

Natural products – modifying metabolite pathways in plants

Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

Computational Analysis of “-omics” Data to Identify Transcription Factors Regulating Secondary Metabolism in Rauvolfia serpentina

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