Functional genomics approach for the discovery of plant-based pharmaceuticals

Research output: Contribution to conferenceOther conference contributionScientific

Abstract

Secondary metabolites of plants exhibit an enormous chemical diversity and include many high-value pharmaceuticals e.g. anticancer drugs. Their production is limited despite the huge demand resulting from the fact that currently about 25% of all pharmaceuticals are plant derived. This is due to the low contents in plants on the one hand and the economically unfeasible chemical synthesis in many cases on the other hand. In contrast to the exploitation of cultured microorganisms plant metabolic engineering has met only limited success, since our knowledge about the biosynthesis of secondary metabolites is still very limited and work with cell cultures is of exceedingly empirical nature. Genetic or enzymatic maps of biosynthetic pathways are mostly missing and the regulation of these pathways is poorly understood. In order to address these problems we have designed a novel approach using tobacco BY-2 cell cultures as a model system, in which a cDNA-AFLP based transcript-profiling technique is linked with targeted metabolic profiling of plant cells to simultaneously identify genes involved in secondary metabolism on a genome-wide scale. From the 20000 transcript tags visualized 591 were jasmonate-modulated with different kinetics. Cluster analysis of expression profiles showed that half of the genes were induced already after 14 hours. These genes were of special interest since accumulation of metabolites started 12 hours after the elicitation. 16% of the tags did not show homology to any known sequence whereas 66% were similar to genes with a known function, and 18% revealed similarity to genes without an allocated function. Functional analysis is performed after the conversion of the gene tags into full-length cDNAs and their cloning into suitable vectors for transformation experiments. The main focus is on genes encoding signal transduction proteins, kinases, phosphatases and transcription factors as well as those with unknown function. Besides identifying several novel genes, we were able to characterize poorly understood branches of secondary metabolite biosynthetic pathways in tobacco, leading to nicotine alkaloids and phenylpropanoids, by using hyphenated analytical tools (GC-, HPLC-MS). The great advantage of this novel technology platform is its universal application to any plant or cell culture of interest without pre-existing gene sequence information.
Original languageEnglish
Number of pages1
Publication statusPublished - 2003
MoE publication typeNot Eligible
EventScanBelt Forum: Workshop 10: Biologically Active Compounds from Plants - , Poland
Duration: 8 May 200310 May 2003

Workshop

WorkshopScanBelt Forum
CountryPoland
Period8/05/0310/05/03

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genomics
drugs
secondary metabolites
genes
cell culture
biochemical pathways
tobacco
metabolic engineering
gene conversion
nicotine
antineoplastic agents
metabolomics
phenylpropanoids
plant cultural practices
protein kinases
amplified fragment length polymorphism
signal transduction
molecular cloning
alkaloids
cluster analysis

Cite this

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title = "Functional genomics approach for the discovery of plant-based pharmaceuticals",
abstract = "Secondary metabolites of plants exhibit an enormous chemical diversity and include many high-value pharmaceuticals e.g. anticancer drugs. Their production is limited despite the huge demand resulting from the fact that currently about 25{\%} of all pharmaceuticals are plant derived. This is due to the low contents in plants on the one hand and the economically unfeasible chemical synthesis in many cases on the other hand. In contrast to the exploitation of cultured microorganisms plant metabolic engineering has met only limited success, since our knowledge about the biosynthesis of secondary metabolites is still very limited and work with cell cultures is of exceedingly empirical nature. Genetic or enzymatic maps of biosynthetic pathways are mostly missing and the regulation of these pathways is poorly understood. In order to address these problems we have designed a novel approach using tobacco BY-2 cell cultures as a model system, in which a cDNA-AFLP based transcript-profiling technique is linked with targeted metabolic profiling of plant cells to simultaneously identify genes involved in secondary metabolism on a genome-wide scale. From the 20000 transcript tags visualized 591 were jasmonate-modulated with different kinetics. Cluster analysis of expression profiles showed that half of the genes were induced already after 14 hours. These genes were of special interest since accumulation of metabolites started 12 hours after the elicitation. 16{\%} of the tags did not show homology to any known sequence whereas 66{\%} were similar to genes with a known function, and 18{\%} revealed similarity to genes without an allocated function. Functional analysis is performed after the conversion of the gene tags into full-length cDNAs and their cloning into suitable vectors for transformation experiments. The main focus is on genes encoding signal transduction proteins, kinases, phosphatases and transcription factors as well as those with unknown function. Besides identifying several novel genes, we were able to characterize poorly understood branches of secondary metabolite biosynthetic pathways in tobacco, leading to nicotine alkaloids and phenylpropanoids, by using hyphenated analytical tools (GC-, HPLC-MS). The great advantage of this novel technology platform is its universal application to any plant or cell culture of interest without pre-existing gene sequence information.",
author = "Heiko Rischer",
year = "2003",
language = "English",
note = "ScanBelt Forum : Workshop 10: Biologically Active Compounds from Plants ; Conference date: 08-05-2003 Through 10-05-2003",

}

Functional genomics approach for the discovery of plant-based pharmaceuticals. / Rischer, Heiko.

2003. ScanBelt Forum, Poland.

Research output: Contribution to conferenceOther conference contributionScientific

TY - CONF

T1 - Functional genomics approach for the discovery of plant-based pharmaceuticals

AU - Rischer, Heiko

PY - 2003

Y1 - 2003

N2 - Secondary metabolites of plants exhibit an enormous chemical diversity and include many high-value pharmaceuticals e.g. anticancer drugs. Their production is limited despite the huge demand resulting from the fact that currently about 25% of all pharmaceuticals are plant derived. This is due to the low contents in plants on the one hand and the economically unfeasible chemical synthesis in many cases on the other hand. In contrast to the exploitation of cultured microorganisms plant metabolic engineering has met only limited success, since our knowledge about the biosynthesis of secondary metabolites is still very limited and work with cell cultures is of exceedingly empirical nature. Genetic or enzymatic maps of biosynthetic pathways are mostly missing and the regulation of these pathways is poorly understood. In order to address these problems we have designed a novel approach using tobacco BY-2 cell cultures as a model system, in which a cDNA-AFLP based transcript-profiling technique is linked with targeted metabolic profiling of plant cells to simultaneously identify genes involved in secondary metabolism on a genome-wide scale. From the 20000 transcript tags visualized 591 were jasmonate-modulated with different kinetics. Cluster analysis of expression profiles showed that half of the genes were induced already after 14 hours. These genes were of special interest since accumulation of metabolites started 12 hours after the elicitation. 16% of the tags did not show homology to any known sequence whereas 66% were similar to genes with a known function, and 18% revealed similarity to genes without an allocated function. Functional analysis is performed after the conversion of the gene tags into full-length cDNAs and their cloning into suitable vectors for transformation experiments. The main focus is on genes encoding signal transduction proteins, kinases, phosphatases and transcription factors as well as those with unknown function. Besides identifying several novel genes, we were able to characterize poorly understood branches of secondary metabolite biosynthetic pathways in tobacco, leading to nicotine alkaloids and phenylpropanoids, by using hyphenated analytical tools (GC-, HPLC-MS). The great advantage of this novel technology platform is its universal application to any plant or cell culture of interest without pre-existing gene sequence information.

AB - Secondary metabolites of plants exhibit an enormous chemical diversity and include many high-value pharmaceuticals e.g. anticancer drugs. Their production is limited despite the huge demand resulting from the fact that currently about 25% of all pharmaceuticals are plant derived. This is due to the low contents in plants on the one hand and the economically unfeasible chemical synthesis in many cases on the other hand. In contrast to the exploitation of cultured microorganisms plant metabolic engineering has met only limited success, since our knowledge about the biosynthesis of secondary metabolites is still very limited and work with cell cultures is of exceedingly empirical nature. Genetic or enzymatic maps of biosynthetic pathways are mostly missing and the regulation of these pathways is poorly understood. In order to address these problems we have designed a novel approach using tobacco BY-2 cell cultures as a model system, in which a cDNA-AFLP based transcript-profiling technique is linked with targeted metabolic profiling of plant cells to simultaneously identify genes involved in secondary metabolism on a genome-wide scale. From the 20000 transcript tags visualized 591 were jasmonate-modulated with different kinetics. Cluster analysis of expression profiles showed that half of the genes were induced already after 14 hours. These genes were of special interest since accumulation of metabolites started 12 hours after the elicitation. 16% of the tags did not show homology to any known sequence whereas 66% were similar to genes with a known function, and 18% revealed similarity to genes without an allocated function. Functional analysis is performed after the conversion of the gene tags into full-length cDNAs and their cloning into suitable vectors for transformation experiments. The main focus is on genes encoding signal transduction proteins, kinases, phosphatases and transcription factors as well as those with unknown function. Besides identifying several novel genes, we were able to characterize poorly understood branches of secondary metabolite biosynthetic pathways in tobacco, leading to nicotine alkaloids and phenylpropanoids, by using hyphenated analytical tools (GC-, HPLC-MS). The great advantage of this novel technology platform is its universal application to any plant or cell culture of interest without pre-existing gene sequence information.

M3 - Other conference contribution

ER -