A5010426642- Plant tissue culture and regeneration
- Alkaloids: synthesis and pharmacology
- Berberine and alkaloids research
- Plant Gene Expression Analysis
- Plant biochemistry and biosynthesis
- Natural product bioactivities and synthesis
- Traditional and Medicinal Uses of Annonaceae
- Phytochemistry and Biological Activities
- Biochemical and biochemical processes
- Chemical synthesis and alkaloids
- Photosynthetic Processes and Mechanisms
- Transgenic Plants and Applications
- Plant Parasitism and Resistance
- Functional Brain Connectivity Studies
- GABA and Rice Research
- Polyamine Metabolism and Applications
- Microbial Natural Products and Biosynthesis
- Microbial Metabolic Engineering and Bioproduction
- Schizophrenia research and treatment
- Plant nutrient uptake and metabolism
- Botanical Research and Chemistry
- Phytochemicals and Antioxidant Activities
- Pharmacogenetics and Drug Metabolism
- Plant Genetic and Mutation Studies
- Microbial bioremediation and biosurfactants
University of Toronto
2005-2025
Centre for Addiction and Mental Health
2017-2025
Mental Health Research Institute
2025
Brock University
2013-2024
St. Michael's Hospital
2024
University of Basilicata
2022
Sapienza University of Rome
2014-2016
Biochemical Society
2012
Université de Montréal
1992-2005
Syngenta (United States)
2001-2005
Plants produce a vast array of specialized metabolites, many which are used as pharmaceuticals, flavors, fragrances, and other high-value fine chemicals. However, most these compounds occur in non-model plants for genomic sequence information is not yet available. The production large amount nucleotide data using next-generation technologies now relatively fast cost-effective, especially when the latest Roche-454 Illumina sequencers with enhanced base-calling accuracy. To investigate...
Antitumor substances related to vinblastine and vincristine are exclusively found in the Catharanthus roseus (Madagascar periwinkle), a member of Apocynaceae plant family, continue be extensively used cancer chemotherapy. Although high demand, these valuable compounds only accumulate trace amounts C. leaves. Vinblastine condensed from monoterpenoid indole alkaloid (MIA) precursors catharanthine vindoline. biosynthesis remains poorly characterized, vindoline MIA precursor tabersonine is well...
In situ RNA hybridization and immunocytochemistry were used to establish the cellular distribution of monoterpenoid indole alkaloid biosynthesis in Madagascar periwinkle (Catharanthus roseus). Tryptophan decarboxylase (TDC) strictosidine synthase (STR1), which are involved central intermediate strictosidine, desacetoxyvindoline 4-hydroxylase (D4H) deacetylvindoline 4-O-acetyltransferase (DAT), terminal steps vindoline biosynthesis, localized. tdc str1 mRNAs present epidermis stems, leaves,...
The sequence of a cDNA clone that includes the complete coding region tryptophan decarboxylase (EC 4.1.1.28, formerly EC 4.1.1.27) from periwinkle (Catharanthus roseus) is reported. (1747 base pairs) was isolated by antibody screening expression library produced poly(A)+ RNA found in developing seedlings C. roseus. hybridized to 1.8-kilobase mRNA and young leaves mature plants. identity confirmed when extracts transformed Escherichia coli expressed protein containing enzyme activity. encodes...
Abstract Catharanthus roseus is the sole commercial source of monoterpenoid indole alkaloids (MIAs), vindoline and catharanthine, components commercially important anticancer dimers, vinblastine vincristine. Carborundum abrasion technique was used to extract leaf epidermis–enriched mRNA, thus sampling epidermome, or complement, proteins expressed in epidermis. Random sequencing derived cDNA library established 3655 unique ESTs, composed 1142 clusters 2513 singletons. Virtually all known MIA...
Summary Alkaloids represent a large and diverse group of compounds that are related by the occurrence nitrogen atom within heterocyclic backbone. Unlike other types secondary metabolites, various structural categories alkaloids unrelated in terms biosynthesis evolution. Although biology each is unique, common patterns have become apparent. Opium poppy ( Papaver somniferum ), which produces several benzylisoquinoline alkaloids, Madagascar periwinkle Catharanthus roseus accumulates an array...
Summary Shortly after germination, alkaloids are rapidly synthesized in seedlings of both Catharanthus roseus L.G. Don and Cinchona ledgeriana Moens. The effect low‐level, atmospheric methyl jasmonate on this developmentally controlled process was studied. In species, about 1 p.p.m. vapor significantly enhanced alkaloid synthesis during resulting a doubling content seedlings. Treatment with resulted increased allocation precursors enzyme activities biosynthesis. ability to increase...
The monoterpenoid indole alkaloids (MIAs) of Madagascar periwinkle ( Catharanthus roseus ) continue to be the most important source natural drugs in chemotherapy treatments for a range human cancers. These anticancer are derived from coupling catharanthine and vindoline yield powerful dimeric MIAs that prevent cell division. However precise mechanisms their assembly within plants remain obscure. Here we report complex development-, environment-, organ-, cell-specific controls involved...
Significance The presence of biologically active monoterpenoid indole alkaloids (MIAs) on the leaf surfaces medicinally important Catharanthus roseus has led to questions about secretion processes involved and their prevalence within MIA-producing species plants. This report shows that a transporter closely related those in cuticle assembly plants belonging pleiotropic drug resistance family ATP-binding cassette transporters is specialized for transport MIA catharanthine surface from its...
Iridoids form a broad and versatile class of biologically active molecules found in thousands plant species. In addition to the many hundreds iridoids occurring plants, some iridoids, such as secologanin, serve key building blocks biosynthesis monoterpene indole alkaloids (MIAs) quinoline alkaloids. This study describes molecular cloning functional characterization three iridoid glucosyltransfeases (UDP-sugar glycosyltransferase6 [UGT6], UGT7, UGT8) from Madagascar periwinkle (Catharanthus...
Significance The multistep assembly of catharanthine and tabersonine from strictosidine remains poorly characterized for understanding the biochemistry anticancer monoterpenoid indole alkaloid (MIA) biosynthesis in medicinal plant, Catharanthus roseus . seven-step pathway 19 E -geissoschizine to four major MIA skeletons enables that complete drugs, anhydrovinblastine vincristine as well production other biologically active MIAs.
Summary The important anticancer drugs, vinblastine, vincristine and analogs, are composed of the monoterpenoid indole alkaloids ( MIA s), catharanthine vindoline, found uniquely in medicinal plant, Catharanthus roseus . While 26 genes involved assembly these two s known, key reactions have eluded characterization to complete documentation vinblastine pathway this plant species. dimeric requires O‐acetylstemmadenine oxidase ASO ) a dual function geissoschizine synthase GS that reduces...
Iridoids are a major group of biologically active molecules that present in thousands plant species, and one versatile iridoid, secologanin, is precursor for the assembly monoterpenoid indole alkaloids (MIAs) as well number quinoline alkaloids. This study uses bioinformatics to screen large databases annotated transcripts from various MIA-producing species select candidate genes may be involved iridoid biosynthesis. Virus-induced gene silencing selected combined with metabolite analyses...
Abstract Hydroxylation of tabersonine at the C-16 position, catalyzed by 16-hydroxylase (T16H), initiates synthesis vindoline that constitutes main alkaloid accumulated in leaves Catharanthus roseus. Over last decade, this reaction has been associated with CYP71D12 cloned from undifferentiated C. roseus cells. In study, we isolated a second cytochrome P450 (CYP71D351) displaying T16H activity. Biochemical characterization demonstrated and CYP71D351 both exhibit high affinity for narrow...
Two early and potential rate-limiting steps in the biosynthesis of isoquinoline alkaloids, such as morphine codeine, opium poppy (Papaver somniferum) involve decarboxylation L-tyrosine L-dihydroxyphenylalanine (L-dopa) to yield tyramine dopamine, respectively. A DNA fragment was amplified by polymerase chain reaction (PCR) using degenerate primers designed two highly conserved domains found other aromatic amino acid decarboxylases. seedling cDNA library screened with this PCR product a...
The creation of artificial metabolic sinks in plants by genetic engineering key branch points may have serious consequences for the pathways being modified. introduction into potato a gene encoding tryptophan decarboxylase (TDC) isolated from Catharanthus roseus drastically altered balance substrate and product pools involved shikimate phenylpropanoid pathways. Transgenic tubers expressing TDC accumulated tryptamine, immediate decarboxylation reaction. redirection tryptamine also resulted...
Vinblastine and vincristine are two medically important bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle). Attempts at production in cell cultures failed because a part of the complex pathway was not active, i.e. tabersonine to vindoline. It starts with 16‐hydroxylase (T16H), cytochrome P450‐dependent enzyme. We now show that T16H is induced suspension culture by light we report cloning cDNA. The enzyme expressed Escherichia coli as translational fusion P450 reductase C. ,...
Summary The biosynthesis of methyl anthranilate, the volatile compound responsible for distinctive ‘foxy’ aroma and flavor Washington Concord grape ( Vitis labrusca ), involves an alcohol acyltransferase that catalyzes formation anthranilate from anthraniloyl‐coenzyme A (CoA) methanol. Although methanol is a poor substrate in comparison with co‐substrate, high levels this (0.5% total protein) combined relatively make reaction possible grapes. This 449 amino acid protein belongs to BAHD...
Hydroxylation at the C-16 position of indole alkaloid tabersonine has been suggested as first step toward vindoline biosynthesis in Catharanthus roseus. Tabersonine 16-hydroxylase (16-OH) activity was detected total protein extracts from young leaves C. roseus using a novel coupled assay system. Enzyme dependent on NADPH and molecular oxygen inhibited by CO, clotrimazole, miconazole, cytochrome c. 16-OH localized to endoplasmic reticulum linear sucrose density gradient centrifugation. These...