Ian A Graham

Ian A Graham
The University of York · Department of Biology

PhD

About

268
Publications
40,396
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Introduction
Ian A Graham is based in the Department of Biology, University of York. His laboratory has used biochemical genetics to understand how oilseeds such as Arabidopsis mobilise their storage reserves and how the oxlipin, OPDA, controls seed germination. His laboratory has used similar approaches to investigate the synthesis of bioactive compounds in some of the world’s major medicinal crops. This has led to new understanding of how genome rearrangement has shaped the evolution of alkaloid metabolism in opium poppy. Characterisation and genetic mapping of traits responsible for production of artemisinin in Artemisia annua has enabled development of F1 hybrid seed that can deliver a robust source of this vital anti-malarial drug for the developing world.
Additional affiliations
September 1999 - present
The University of York
Position
  • Chair of Biochemical Genetics

Publications

Publications (268)
Article
Full-text available
The STORR gene fusion event is considered essential for the evolution of the promorphinan/morphinan subclass of benzylisoquinoline alkaloids (BIAs) in opium poppy as the resulting bi-modular protein performs the isomerization of (S)- to (R)-reticuline essential for their biosynthesis. Here, we show that of the 12 Papaver species analysed those cont...
Article
Full-text available
Secondary metabolism in plants gives rise to a vast array of small-molecule natural products. The discovery of operon-like gene clusters in plants has provided a new perspective on the evolution of specialized metabolism and the opportunity to rapidly advance the metabolic engineering of natural product production. Here, we review historical aspect...
Article
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Maf1 is a transcription factor that is conserved in sequence and structure between yeasts, animals and plants. Its principal molecular function is also well conserved, being to bind and repress RNA polymerase (pol) III, thereby inhibiting synthesis of tRNAs and other noncoding RNAs. Restrictions on tRNA production and hence protein synthesis can pr...
Preprint
Full-text available
The STORR gene fusion event is considered a key step in the evolution of benzylisoquinoline alkaloid (BIA) metabolism in opium poppy as the resulting bi-modular protein performs the isomerization of ( S )- to ( R )-reticuline which is required for morphinan biosynthesis. Our previous analysis of the opium poppy genome suggested the STORR gene fusio...
Article
Full-text available
Diterpene biosynthesis commonly originates with the methylerythritol phosphate (MEP) pathway in chloroplasts, leading to the C20 substrate, geranylgeranyl pyrophosphate (GGPP). The previous work demonstrated that over-expression of genes responsible for the first and last steps in the MEP pathway in combination with GERANYLGERANYL PYROPHOSPHATE SYN...
Article
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Traditional crops historically provided accessible and affordable nutrition to millions of rural dwellers but have been neglected, with most modern agricultural systems over reliant on a small number of internationally-traded crops. Traditional crops are typically well-adapted to local agro-ecological conditions and many are nutrient-dense. They ca...
Article
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To engineer Nicotiana benthamiana to produce novel diterpenoids, we first aimed to increase production of the diterpenoid precursor geranylgeranyl pyrophosphate (GGPP) by upregulation of key genes of the non‐mevalonate (MEP) pathway sourced from Arabidopsis thaliana. We used transient expression to evaluate combinations of the eight MEP pathway gen...
Article
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A Correction to this paper has been published: https://doi.org/10.1038/s41477-020-00838-1.
Article
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19 we report the discovery of a rice diterpenoid gene cluster on chromosome 7 (DGC7) 20 encoding the entire biosynthetic pathway to 5,10-diketo-casbene, a member of 21 the mono-cyclic casbene-derived diterpenoids. We revealed that DGC7 is 22 regulated through MeJA mediated epigenetic control directly by JMJ705 3. 23 Functional characterization of p...
Article
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Diterpenoids are the major group of antimicrobial phytoalexins in rice1,2. Here, we report the discovery of a rice diterpenoid gene cluster on chromosome 7 (DGC7) encoding the entire biosynthetic pathway to 5,10-diketo-casbene, a member of the monocyclic casbene-derived diterpenoids. We revealed that DGC7 is regulated directly by JMJ705 through met...
Article
Full-text available
Many modern rice varieties have been intensively selected for high‐yielding performance under irrigated conditions, reducing their genetic diversity and potentially increasing their susceptibility to abiotic stresses such as drought. In this study, we tested benefits for stress tolerance of introducing DNA segments from wild ancestor Oryza rufipogo...
Article
Full-text available
Phylogenomic analysis of whole genome sequences of five benzylisoquinoline alkaloid (BIA)-producing species from the Ranunculales and Proteales orders of flowering plants revealed the sequence and timing of evolutionary events leading to the diversification of these compounds. (S)-Reticuline is a pivotal intermediate in the synthesis of many BIAs a...
Article
Light quality plays vital roles in the life cycle of plants. For example, in seeds of many species, light quality determines the levels of the gibberelins (GA) and abscisic acid (ABA) phytohormones, which promote and repress seed germination respectively (Seo et al., 2006). In Arabidopsis thaliana, the photoreceptors phytochrome A (PHYA) and PHYB d...
Article
Full-text available
Light-dependent seed germination is induced by gibberellins (GA) and inhibited by abscisic acid (ABA). The widely accepted view of GA/ABA ratio controlling germination does not however explain the fact that seeds deficient in ABA still germinate poorly under shade light conditions that repress germination. In Arabidopsis, MOTHER-OF-FT-AND-TFL1 (MFT...
Article
Full-text available
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for uncomplicated malaria caused by Plasmodium falciparum parasites. Other metabolites in A. annua or related species, particularly flavonoids, have been proposed to either act as antimalarials on...
Article
The opium poppy, Papaver somniferum, has been a source of medicinal alkaloids since the earliest civilizations; ca. 3400 B.C. The benzylisoquinoline alkaloid noscapine is produced commercially in P. somniferum for use as a cough suppressant and it also has potential as an anticancer compound. The first committed step in the recently elucidated nosc...
Article
In Arabidopsis, seed germination is a biphasic process involving rupture of the seed coat followed by emergence of the radicle through the micropylar endosperm. Embryo expansion results in seed coat rupture and removal of seed coat imposed dormancy with DELLA proteins blocking embryo expansion in the absence of gibberellins. Exogenous abscisic acid...
Article
Full-text available
Plant response to environmental stimuli involves integration of multiple signals. Upon low-oxygen stress, plants initiate a set of adaptive responses to circumvent an energy crisis. Here, we reveal how these stress responses are induced by combining (i) energy-dependent changes in the composition of the acyl-CoA pool and (ii) the cellular oxygen co...
Data
Figure S1. Barley leaves and leaf zones. A: Numbering of leaves. B: Leaf segments of second leaf harvested for the analysis Figure S2. Pathogen symptoms and inoculation procedure. A: Lesions caused by R. commune 12 days after inoculation. B: Colonies of B. graminis 12 days after inoculation. C: Setup for applying B. graminis spores to leaf segments...
Article
Full-text available
Morphinan-based painkillers are derived from opium poppy. We report a draft of the opium poppy genome, with 2.72 Gb assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 Mb and 204 Mb, respectively. Synteny analysis suggests a whole genome duplication at approximately 7.8 million years ago (MYA) and ancient segmental or whole genom...
Article
Full-text available
Seed germination in many plant species is triggered by sunlight, which is rich in the red (R) wavelength and repressed by under- the-canopy light rich in far red (FR). R:FR ratios are sensed by phytochromes to regulate levels of gibberellins (GAs) and abscisic acid (ABA), which induce and inhibit germination respectively. In this study we have disc...
Article
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Understanding the interactions between mineral nutrition and disease is essential for crop management. Our previous studies with Arabidopsis thaliana demonstrated that potassium (K) deprivation induced the biosynthesis of jasmonate (JA) and increased the plant's resistance to herbivorous insects. Here we addressed the question how tissue K affects...
Article
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Chemical derivatives of artemisinin, a sesquiterpene lactone produced by Artemisia annua, are the active ingredient in the most effective treatment for malaria. Comprehensive phytochemical analysis of two contrasting chemotypes of A. annua resulted in the characterization of over 80 natural products by NMR, more than 20 of which are novel and descr...
Article
Full-text available
Artemisia annua is established as an efficient crop for the production of the anti-malarial compound artemisinin, a sesquiterpene lactone synthesized and stored in Glandular Secretory Trichomes (GSTs) located on the leaves and inflorescences. Amorpha-4,11-diene synthase (AMS) catalyzes the conversion of farnesyl pyrophosphate (FPP) to amorpha-4,11-...
Article
Full-text available
Phenolic composition of virgin olive oil is determined by the enzymatic and/or chemical reactions that take place during olive fruit processing. Of these enzymes, β-glucosidase activity plays a relevant role in the transformation of the phenolic glycosides present in the olive fruit, generating different secoiridoid derivatives. The main goal of th...
Article
Full-text available
Recent advances in the area of genomics have led to the development of high throughput genotyping platforms that have immensely contributed to molecular breeding programs. Custom-designed single nucleotide polymorphism (SNP) arrays provide an efficient, cost effective, high throughput genotyping tool for QTL/gene mapping, variety identification, ma...
Article
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for malaria currently available. We identified a mutation that disrupts the amorpha-4,11-diene C-12 oxidase (CYP71AV1) enzyme, responsible for a series of oxidation reactions in the artemisinin bio...
Article
Full-text available
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in the most effective treatment for malaria currently available. We identified a mutation that disrupts the amorpha-4,11-diene C-12 oxidase (CYP71AV1) enzyme, responsible for a series of oxidation reactions in the artemisinin bio...
Article
Full-text available
The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids w...
Article
Full-text available
We previously demonstrated that the oxylipin 12-oxo-phytodienoic acid (OPDA) acts along with abscisic acid to regulate seed germination in Arabidopsis thaliana, but the mechanistic details of this synergistic interaction remain to be elucidated. Here, we show that OPDA acts through the germination inhibition effects of abscisic acid, the abscisic a...
Article
Full-text available
Stomata regulate the uptake of CO2 and the loss of water vapor [1] and contribute to the control of water-use efficiency [2] in plants. Although the guard-cell-signaling pathway coupling blue light perception to ion channel activity is relatively well understood [3], we know less about the sources of ATP required to drive K+ uptake [3–6]. Here, we...
Article
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The health and wellbeing of future generations will depend on humankind's ability to deliver sufficient nutritious food to a world population in excess of 9 billion. Feeding this many people by 2050 will require science-based solutions that address sustainable agricultural productivity and enable healthful dietary patterns in a more globally equita...
Article
Full-text available
Background Economical cultivation of the oilseed crop Jatropha curcas is currently hampered in part due to the non-availability of purpose-bred cultivars. Although genetic maps and genome sequence data exist for this crop, marker-assisted breeding has not yet been implemented due to a lack of available marker–trait association studies. To identify...
Article
As seasons change, dormant seeds cycle through dormant states until the environmental conditions are favorable for seedling establishment. Dormancy cycle is widespread in the plant kingdom allowing the seeds to display primary and secondary dormancy. Several reports in the last decade have focused on understanding the molecular mechanisms of primar...
Article
Morphinan alkaloids from opium poppy are used for pain relief. Direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)- reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the l...
Article
Full-text available
Seasonal behavior is important for fitness in temperate environments but it is unclear how progeny gain their initial seasonal entrainment. Plants use temperature signals to measure time of year, and changes to life histories are therefore an important consequence of climate change. Here we show that in Arabidopsis the current and prior temperature...
Article
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The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the tr...
Article
Fats based on stearic acid could be a healthier alternative to existing oils especially hydrogenated fractions of oils or palm, but only a few non-tropical species produce oils with these characteristics. In this regard, newly developed high stearic oilseed crops could be a future source of fats and hard stocks rich in stearic and oleic fatty acids...
Article
Full-text available
We used expressed sequence tag library and whole genome sequence mining to identify a suite of putative desaturase genes representing the four main activities required for production of polyunsaturated fatty acids in hemp seed oil. Phylogenetic-based classification and developing seed transcriptome analysis informed selection for further analysis o...
Article
Full-text available
The substrate specificity of the acyl-acyl carrier protein (ACP) thioesterases significantly determines the type of fatty acids that are exported from plastids. Thus, designing acyl-ACP thioesterases with different substrate specificities or kinetic properties would be of interest for plant lipid biotechnology to produce oils enriched in specialty...
Data
##Assembly-Data-START## Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##
Data
##Assembly-Data-START## Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##
Article
Fatty acid β-oxidation is an essential process in many aspects of plant development, and storage oil in the form of triacylglycerol (TAG) is an important food source for humans and animals, for biofuel and for industrial feedstocks. In this study we characterize the effects of a small molecule, diphenyl methylphosphonate, on oil mobilization in Ara...
Article
Full-text available
Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring 'nontoxic' provenances exist which produce seed lacki...
Data
File S4 Markers used to bridge the maps produced in this study with the previously published map produced from an interspecific cross between J. curcas and J. integerrima (Wang.,).