Alkaloids Biosynthesis

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Kexuan Tang - One of the best experts on this subject based on the ideXlab platform.

  • monoterpenoid indole Alkaloids Biosynthesis and its regulation in catharanthus roseus a literature review from genes to metabolites
    Phytochemistry Reviews, 2016
    Co-Authors: Qifang Pan, Kexuan Tang, Natali Rianika Mustafa, Young Hae Choi, Robert Verpoorte
    Abstract:

    As the only source for the low-abundance antitumor agents vinblastine and vincristine, Catharanthus roseus is highly valued and has been studied extensively as a model for medicinal plants improvement. The Biosynthesis of these monoterpenoid indole Alkaloids (MIAs) is a complex multistep enzymatic network that is tightly regulated by developmental and environmental factors. Here we review the knowledge achieved in the past 30 years of the MIA pathway in C. roseus, from genetic to metabolic aspects. Two early precursor pathways and a late mono-/bis-indole alkaloid pathway have been largely elucidated and established, as well as their intercellular and subcellular compartmentation. Many genes encoding constitutive structural biosynthetic enzymes, transcription factors, and transporters involved in these pathways have been cloned, characterized and applied in metabolic engineering strategies to improve the MIA production. However, genetic modification in the pathway in C. roseus resulted in complicated changes of both secondary and primary metabolism, affecting not only the MIA pathway but also other pathways. Research at metabolic level is required to increase the knowledge on the genetic regulation of the whole metabolic network connected to the MIA Biosynthesis. Nuclear magnetic resonance-based metabolomics (metabolic profiling, fingerprinting and flux analyses) in combination with other “omics” have been implemented in studies of C. roseus for pathway elucidation, including among others, understanding stress response, cross talk between pathways, and diversion of carbon fluxes, with the aim to fully unravel the MIA Biosynthesis, its regulation and the function of the Alkaloids in the plant from a systems biology point of view.

  • terpenoid indole Alkaloids Biosynthesis and metabolic engineering in catharanthus roseus
    Journal of Integrative Plant Biology, 2007
    Co-Authors: Donghui Liu, Hongbin Jin, Yuhui Chen, Lijie Cui, Weiwei Ren, Yifu Gong, Kexuan Tang
    Abstract:

    Catharanthus roseus L. (Madagascar periwinkle) biosynthesizes a diverse array of secondary metabolites including anticancer dimeric Alkaloids (vinblastine and vincristine) and antihypertensive Alkaloids (ajmalicine and serpentine). The multi-step terpenoid indole Alkaloids (TIAs) biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs Biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs Biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs Biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.

  • Metabolic Engineering of Tropane Alkaloid Biosynthesis in Plants
    Journal of Integrative Plant Biology, 2005
    Co-Authors: Lei Zhang, Guoyin Kai, Kexuan Tang, Hanming Zhang, Ji-hong Jiang, Wansheng Chen
    Abstract:

    : 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. ( Managing editor: Wei WANG)

Robert Verpoorte - One of the best experts on this subject based on the ideXlab platform.

  • monoterpenoid indole Alkaloids Biosynthesis and its regulation in catharanthus roseus a literature review from genes to metabolites
    Phytochemistry Reviews, 2016
    Co-Authors: Qifang Pan, Kexuan Tang, Natali Rianika Mustafa, Young Hae Choi, Robert Verpoorte
    Abstract:

    As the only source for the low-abundance antitumor agents vinblastine and vincristine, Catharanthus roseus is highly valued and has been studied extensively as a model for medicinal plants improvement. The Biosynthesis of these monoterpenoid indole Alkaloids (MIAs) is a complex multistep enzymatic network that is tightly regulated by developmental and environmental factors. Here we review the knowledge achieved in the past 30 years of the MIA pathway in C. roseus, from genetic to metabolic aspects. Two early precursor pathways and a late mono-/bis-indole alkaloid pathway have been largely elucidated and established, as well as their intercellular and subcellular compartmentation. Many genes encoding constitutive structural biosynthetic enzymes, transcription factors, and transporters involved in these pathways have been cloned, characterized and applied in metabolic engineering strategies to improve the MIA production. However, genetic modification in the pathway in C. roseus resulted in complicated changes of both secondary and primary metabolism, affecting not only the MIA pathway but also other pathways. Research at metabolic level is required to increase the knowledge on the genetic regulation of the whole metabolic network connected to the MIA Biosynthesis. Nuclear magnetic resonance-based metabolomics (metabolic profiling, fingerprinting and flux analyses) in combination with other “omics” have been implemented in studies of C. roseus for pathway elucidation, including among others, understanding stress response, cross talk between pathways, and diversion of carbon fluxes, with the aim to fully unravel the MIA Biosynthesis, its regulation and the function of the Alkaloids in the plant from a systems biology point of view.

  • catharanthus terpenoid indole Alkaloids Biosynthesis and regulation
    Phytochemistry Reviews, 2007
    Co-Authors: Magdi A Elsayed, Robert Verpoorte
    Abstract:

    Catharanthus roseus is still the only source for the powerful antitumour drugs vinblastine and vincristine. Some other pharmaceutical compounds from this plant, ajmalicine and serpentine are also of economical importance. Although C. roseus has been studied extensively and was subject of numerous publications, a full characterization of its alkaloid pathway is not yet achieved. Here we review some of the recent work done on this plant. Most of the work focussed on early steps of the pathway, particularly the discovery of the 2-C-methyl-d-erythritol 4-phosphate (MEP)-pathway leading to terpenoids. Both mevalonate and MEP pathways are utilized by plants with apparent cross-talk between them across different compartments. Many genes of the early steps in Catharanthus alkaloid pathway have been cloned and overexpressed to improve the Biosynthesis. Research on the late steps in the pathway resulted in cloning of several genes. Enzymes and genes involved in indole alkaloid Biosynthesis and various aspects of their localization and regulation are discussed. Much progress has been made at alkaloid regulatory level. Feeding precursors, growth regulators treatments and metabolic engineering are good tools to increase productivity of terpenoid indole Alkaloids. But still our knowledge of the late steps in the Catharanthus alkaloid pathway and the genes involved is limited.

Guoyin Kai - One of the best experts on this subject based on the ideXlab platform.

  • Transcriptome exploration for further understanding of the tropane Alkaloids Biosynthesis in Anisodus acutangulus
    Molecular genetics and genomics : MGG, 2015
    Co-Authors: Lijie Cui, Pan Liao, Fenfen Huang, Dasheng Zhang, Yuping Lin, Jie Zong, Guoyin Kai
    Abstract:

    Tropane Alkaloids (TAs) such as anisodamine, anisodine, hyoscyamine and scopolamine are extensively used in clinical practice as anticholinergic agents. Anisodus acutangulus produces TAs in root tissue, and although several genes involved in scopolamine Biosynthesis have been cloned, yet the biosynthetic pathway of TAs remains poorly understood. To further understand TAs Biosynthesis mechanism, transcriptome analysis with deep RNA sequencing in A. acutangulus roots was performed in this study; 48 unigenes related to tropane, piperidine and pyridine alkaloid Biosynthesis, 145 linked to the distribution of arginine to TAs Biosynthesis, and 86 categorized to terpenoid backbone Biosynthesis have been identified in pathway enrichment analyses with eukaryotic orthologous groups (KOG) and Kyoto encyclopedia of genes and genomes. Additionally, 82 unigenes annotated as cytochrome P450 family members seemed to be involved in secondary metabolism. Genes encoding littorine mutase/monooxygenase (CYP80F1), diamine oxidase (DAO), alcohol dehydrogenase (ADH) and aromatic amino acid aminotransferase (ArAT) may also play roles in TAs biosynthetic pathways. Furthermore, over 1,000 unigenes were identified as potential transcription factors of WRKY, AP2/ERF, MYB and bHLH families, which would be helpful to understand transcriptional regulation of secondary metabolite Biosynthesis. These data enable novel insights into A. acutangulus transcriptome, updating the knowledge of TAs biosynthetic mechanism at molecular level.

  • Molecular characterization and expression analysis of two distinct putrescine N-methyltransferases from roots of Anisodus acutangulus
    Physiologia plantarum, 2008
    Co-Authors: Guoyin Kai, Yan Zhang, Junfeng Chen, Xiangming Yan, Ran Zhang, Pan Liao, Wei Wang, Genyu Zhou
    Abstract:

    Putrescine N-methyltransferase (PMT; EC. 2.5.1.53) catalyzes the S-adenosylmethionine-dependent N-methylation of putrescine to form N-methylputrescine, which was the first committed step in tropane alkaloid biosynthetic pathway. Two PMT cDNA clones [Anisodus acutangulus putrescine N-methyltransferase 1 (AaPMT1), GenBank Accession No. EU670745; AaPMT2, GenBank Accession No. EU670746] were obtained and characterized together from Anisodus acutangulus for the first time. The full-length cDNA of AaPMT1 was 1322 bp containing a 1014-bp open reading frame (ORF) encoding a polypeptide of 338 amino acids and AaPMT2 was 1219 bp containing a 1041-bp ORF encoding a polypeptide of 347 amino acids. Comparison of the deduced amino acid sequences of AaPMTs with those from tropane alkaloid-producing plants revealed that AaPMTs had high similarity with other plants PMT. Phylogenetic tree analysis displayed that AaPMT1 showed extensive homology with PMT from Anisodus tanguticus, and AaPMT2 had closer relationship with PMT2 from Atropa belladonna, which indicated PMTs belonged to PMT superfamily. Southern hybridization analysis of the genomic DNA revealed the occurrence of two PMT copies in A. acutangulus genome. Tissue expression pattern analysis revealed that AaPMT1 expressed strongly in roots, weakly in steams and leaves, besides, AaPMT2 presented a similar weaker trend. It indicated that AaPMTs were constitutive expression genes, which were the first reported tissue-independent PMT genes compared with other known PMT genes. AaPMT1 expression was upregulated by methyl jasmonate (MeJA) in all tissues, reaching the highest level after 24 h of the treatment. AaPMT2 also exhibited a very similar trend, whereas the expression was much weaker than that in AaPMT1. So, AaPMTs were considered to be MeJA elicitor-responsive genes and could be effectively elicited at least at the transcriptional level. The work would provide useful knowledge for tropane Alkaloids Biosynthesis and metabolic engineering to increase the production.

  • Metabolic Engineering of Tropane Alkaloid Biosynthesis in Plants
    Journal of Integrative Plant Biology, 2005
    Co-Authors: Lei Zhang, Guoyin Kai, Kexuan Tang, Hanming Zhang, Ji-hong Jiang, Wansheng Chen
    Abstract:

    : 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. ( Managing editor: Wei WANG)

Donghui Liu - One of the best experts on this subject based on the ideXlab platform.

  • terpenoid indole Alkaloids Biosynthesis and metabolic engineering in catharanthus roseus
    Journal of Integrative Plant Biology, 2007
    Co-Authors: Donghui Liu, Hongbin Jin, Yuhui Chen, Lijie Cui, Weiwei Ren, Yifu Gong, Kexuan Tang
    Abstract:

    Catharanthus roseus L. (Madagascar periwinkle) biosynthesizes a diverse array of secondary metabolites including anticancer dimeric Alkaloids (vinblastine and vincristine) and antihypertensive Alkaloids (ajmalicine and serpentine). The multi-step terpenoid indole Alkaloids (TIAs) biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs Biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs Biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs Biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.

Magdi A Elsayed - One of the best experts on this subject based on the ideXlab platform.

  • catharanthus terpenoid indole Alkaloids Biosynthesis and regulation
    Phytochemistry Reviews, 2007
    Co-Authors: Magdi A Elsayed, Robert Verpoorte
    Abstract:

    Catharanthus roseus is still the only source for the powerful antitumour drugs vinblastine and vincristine. Some other pharmaceutical compounds from this plant, ajmalicine and serpentine are also of economical importance. Although C. roseus has been studied extensively and was subject of numerous publications, a full characterization of its alkaloid pathway is not yet achieved. Here we review some of the recent work done on this plant. Most of the work focussed on early steps of the pathway, particularly the discovery of the 2-C-methyl-d-erythritol 4-phosphate (MEP)-pathway leading to terpenoids. Both mevalonate and MEP pathways are utilized by plants with apparent cross-talk between them across different compartments. Many genes of the early steps in Catharanthus alkaloid pathway have been cloned and overexpressed to improve the Biosynthesis. Research on the late steps in the pathway resulted in cloning of several genes. Enzymes and genes involved in indole alkaloid Biosynthesis and various aspects of their localization and regulation are discussed. Much progress has been made at alkaloid regulatory level. Feeding precursors, growth regulators treatments and metabolic engineering are good tools to increase productivity of terpenoid indole Alkaloids. But still our knowledge of the late steps in the Catharanthus alkaloid pathway and the genes involved is limited.