A5024537880- Alkaloids: synthesis and pharmacology
- Plant biochemistry and biosynthesis
- Microbial Natural Products and Biosynthesis
- Plant tissue culture and regeneration
- Chemical synthesis and alkaloids
- Berberine and alkaloids research
- Phytochemistry and Biological Activities
- Traditional and Medicinal Uses of Annonaceae
- Carbohydrate Chemistry and Synthesis
- Natural product bioactivities and synthesis
- Photosynthetic Processes and Mechanisms
- Transgenic Plants and Applications
- Enzyme Catalysis and Immobilization
- Plant and fungal interactions
- Pharmacological Effects of Natural Compounds
- Plant Parasitism and Resistance
- Genomics and Phylogenetic Studies
- Fungal Biology and Applications
- Microbial Metabolic Engineering and Bioproduction
- Phytochemical Studies and Bioactivities
- Glycosylation and Glycoproteins Research
- Plant and animal studies
- Steroid Chemistry and Biochemistry
- Cancer Treatment and Pharmacology
- Chemical Synthesis and Analysis
Max Planck Institute for Chemical Ecology
2019-2025
University of Naples Federico II
2024
Utrecht University
2022
John Innes Centre
2010-2019
Norwich Research Park
2012-2019
Norwich University
2015-2016
Evolva (Switzerland)
2015
Boston University
2015
Sainsbury Laboratory
2015
University of East Anglia
2011-2013
Significance Plants make a wide variety of complex molecules with potent biological activities including several anticancer therapeutics. Unfortunately, plants often produce these in low amounts, making them expensive to obtain. Engineering simpler organisms, such as yeast, plant-derived compounds provides one solution production challenges. One group molecules, the monoterpene indole alkaloids, is synthesized from common intermediate, strictosidine. Here, we report how developed yeast...
The Madagascar periwinkle, Catharanthus roseus, belongs to the Apocynaceae family.This medicinal plant, endemic Madagascar, produces many important drugs including monoterpene indole alkaloids (MIA) vincristine and vinblastine used treat cancer worldwide.Here, we provide a new version of C. roseus genome sequence obtained through combination Oxford Nanopore Technologies long-reads Illumina short-reads.This more contiguous assembly consists 173 scaffolds with total length 581.128Mb an N50...
How to make bioactive alkaloids Vinblastine and vincristine are important, expensive anticancer agents that produced by dimerization of the plant-derived catharanthine vindoline. The enzymes transform tabersonine into vindoline known; however, mechanism which scaffolds generated has been a mystery. Caputi et al. now describe biosynthetic genes corresponding responsible. This resolves long-standing question how plant alkaloid synthesized, is important not only for vinblastine biosynthesis,...
Abstract Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine 1 . As MIAs difficult to chemically synthesize, world’s supply chain for relies on low-yielding extraction purification precursors vindoline catharanthine from Catharanthus roseus , which is then followed by simple in vitro chemical coupling reduction form at an industrial scale...
Inventors in the field of mechanical and electronic engineering can access multitudes components and, thanks to standardization, parts from different manufacturers be used combination with each other. The introduction BioBrick standards for assembly characterized DNA sequences was a landmark microbial engineering, shaping synthetic biology. Here, we describe standard Type IIS restriction endonuclease-mediated assembly, defining common syntax 12 fusion sites enable facile eukaryotic...
The medicinal plant Madagascar periwinkle, Catharanthus roseus (L.) G. Don, produces hundreds of biologically active monoterpene-derived indole alkaloid (MIA) metabolites and is the sole source potent, expensive anti-cancer compounds vinblastine vincristine. Access to a genome sequence would enable insights into biochemistry, control, evolution genes responsible for MIA biosynthesis. However, generation near-complete, scaffolded prohibitive small research communities due expense, time,...
Plants make specialized bioactive metabolites to defend themselves against attackers. The conserved control mechanisms are based on transcriptional activation of the respective plant species-specific biosynthetic pathways by phytohormone jasmonate. Knowledge transcription factors involved, particularly in terpenoid biosynthesis, remains fragmentary. By transcriptome analysis and functional screens medicinal Catharanthus roseus (Madagascar periwinkle), unique source monoterpenoid indole...
Strychnine is a natural product that, through isolation, structural elucidation and synthetic efforts, shaped the field of organic chemistry. Currently, strychnine used as pesticide to control rodents
Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection transcripts and metabolites at level single cells high-resolution determination gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated monoterpene indole alkaloid (MIA) biosynthetic pathway Catharanthus roseus, source leading anticancer drugs. We identified clusters genes involved MIA biosynthesis on eight C. roseus chromosomes extensive duplication...
The Pictet−Spengler reaction, which yields either a β-carboline or tetrahydroquinoline product from an aromatic amine and aldehyde, is widely utilized in plant alkaloid biosynthesis. Here we deconvolute the role that biosynthetic enzyme strictosidine synthase plays catalyzing stereoselective synthesis of product. Notably, rate-controlling step mechanism, as identified by appearance primary kinetic isotope effect (KIE), rearomatization positively charged intermediate. KIE nonenzymatic...
The natural diversity of plant metabolism has long been a source for human medicines. One group plant-derived compounds, the monoterpene indole alkaloids (MIAs), includes well-documented therapeutic agents used in treatment cancer (vinblastine, vincristine, camptothecin), hypertension (reserpine, ajmalicine), malaria (quinine), and as analgesics (7-hydroxymitragynine). Our understanding biochemical pathways that synthesize these commercially relevant compounds is incomplete due part to lack...
Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances technology, but it is difficult gauge current capabilities identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", which 3 months were given build produce 10 molecules unknown us advance. By applying diversity of new approaches, we produced...
Monoterpene indole alkaloids comprise a diverse family of over 2000 plant-produced natural products. This pathway provides an outstanding example how nature creates chemical diversity from single precursor, in this case the intermediate strictosidine. The enzymes that elicit these seemingly disparate products strictosidine have hitherto been elusive. Here we show concerted action two commonly involved product metabolism-an alcohol dehydrogenase and cytochrome P450-produces unexpected...
<h2>Abstract</h2> The evolution of chemical complexity has been a major driver plant diversification, with novel compounds serving as key innovations. species-rich mint family (Lamiaceae) produces an enormous variety that act attractants and defense molecules in nature are used widely by humans flavor additives, fragrances, anti-herbivory agents. To elucidate the mechanisms which such diversity evolved, we combined leaf transcriptome data from 48 Lamiaceae species four outgroups robust...