The John Innes Centre Publications Repository contains details of all publications resulting from our researchers.

The repository also includes Open Access publications, which can be identified by the icons found on search results.

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The creation of this publications repository was funded by BBSRC.

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Leveau A., Reed J., Qiao X., Stephenson M. J., Mugford S. T., Melton R. E., Rant J. C., Vickerstaff R., Langdon T., Osbourn A. (2018)

Towards take-all control: a C-21ß oxidase required for acylation of triterpene defence compounds in oat.

New Phytologist

Publisher's version: 10.1111/nph.15456

ID: 59776

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Oats produce avenacins, antifungal triterpenes that are synthesized in the roots and provide protection against take-all and other soilborne diseases. Avenacins are acylated at the carbon-21 position of the triterpene scaffold, a modification critical for antifungal activity. We have previously characterized several steps in the avenacin pathway, including those required for acylation. However, transfer of the acyl group to the scaffold requires the C-21ß position to be oxidized first, by an as yet uncharacterized enzyme. We mined oat transcriptome data to identify candidate cytochrome P450 enzymes that may catalyse C-21ß oxidation. Candidates were screened for activity by transient expression in Nicotiana benthamiana. We identified a cytochrome P450 enzyme AsCYP72A475 as a triterpene C-21ß hydroxylase, and showed that expression of this enzyme together with early pathway steps yields C-21ß oxidized avenacin intermediates. We further demonstrate that AsCYP72A475 is synonymous with Sad6, a previously uncharacterized locus required for avenacin biosynthesis. sad6 mutants are compromised in avenacin acylation and have enhanced disease susceptibility. The discovery of AsCYP72A475 represents an important advance in the understanding of triterpene biosynthesis and paves the way for engineering the avenacin pathway into wheat and other cereals for control of take-all and other diseases.

Nützmann H. W., Scazzocchio C., Osbourn A. (2018)

Metabolic Gene Clusters in Eukaryotes.

Annual Review of Genetics

Publisher's version: 10.1146/annurev-genet-120417-031237

ID: 59656

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In bacteria, more than half of the genes in the genome are organized in operons. In contrast, in eukaryotes, functionally related genes are usually dispersed across the genome. There are, however, numerous examples of functional clusters of nonhomologous genes for metabolic pathways in fungi and plants. Despite superficial similarities with operons (physical clustering, coordinate regulation), these clusters have not usually originated by horizontal gene transfer from bacteria, and (unlike operons) the genes are typically transcribed separately rather than as a single polycistronic message. This clustering phenomenon raises intriguing questions about the origins of clustered metabolic pathways in eukaryotes and the significance of clustering for pathway function. Here we review metabolic gene clusters from fungi and plants, highlight commonalities and differences, and consider how these clusters form and are regulated. We also identify opportunities for future research in the areas of large-scale genomics, synthetic biology, and experimental evolution. Expected final online publication date for the Annual Review of Genetics Volume 52 is November 23, 2018. Please see for revised estimates.

Stephenson M. J., Reed J., Brouwer B., Osbourn A. (2018)

Transient expression in Nicotiana Benthamiana leaves for triterpene production at a preparative scale.

Journal of visualized experiments : JoVE

Publisher's version: 10.3791/58169

ID: 59691

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The triterpenes are one of the largest and most structurally diverse families of plant natural products. Many triterpene derivatives have been shown to possess medicinally relevant biological activity. However, thus far this potential has not translated into a plethora of triterpene-derived drugs in the clinic. This is arguably (at least partially) a consequence of limited practical synthetic access to this class of compound, a problem that can stifle the exploration of structure-activity relationships and development of lead candidates by traditional medicinal chemistry workflows. Despite their immense diversity, triterpenes are all derived from a single linear precursor, 2,3-oxidosqualene. Transient heterologous expression of biosynthetic enzymes in N. benthamiana can divert endogenous supplies of 2,3-oxidosqualene towards the production of new high-value triterpene products that are not naturally produced by this host. Agro-infiltration is an efficient and simple means of achieving transient expression in N. benthamiana. The process involves infiltration of plant leaves with a suspension of Agrobacterium tumefaciens carrying the expression construct(s) of interest. Co-infiltration of an additional A. tumefaciens strain carrying an expression construct encoding an enzyme that boosts precursor supply significantly increases yields. After a period of five days, the infiltrated leaf material can be harvested and processed to extract and isolate the resulting triterpene product(s). This is a process that is linearly and reliably scalable, simply by increasing the number of plants used in the experiment. Herein is described a protocol for rapid preparative-scale production of triterpenes utilizing this plant-based platform. The protocol utilizes an easily replicable vacuum infiltration apparatus, which allows the simultaneous infiltration of up to four plants, enabling batch-wise infiltration of hundreds of plants in a short period of time.

Li Y., Wang R., Xun X., Wang J., Bao L., Thimmappa R., Ding J., Jiang J., Zhang L., Li T., Lv J., Mu C., Hu X., Zhang L., Liu J., Li Y., Yao L., Jiao W., Wang Y., Lian S., Zhao Z., Zhan Y., Huang X., Liao H., Wang J., Sun H., Mi X., Xia Y., Xing Q., Lu W., Osbourn A., Zhou Z., Chang Y., Bao Z., Wang S. (2018)

Sea cucumber genome provides insights into saponin biosynthesis and aestivation regulation.

Cell discovery (4) 29

Publisher's version: 10.1038/s41421-018-0030-5

ID: 59379

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Echinoderms exhibit several fascinating evolutionary innovations that are rarely seen in the animal kingdom, but how these animals attained such features is not well understood. Here we report the sequencing and analysis of the genome and extensive transcriptomes of the sea cucumber Apostichopus japonicus, a species from a special echinoderm group with extraordinary potential for saponin synthesis, aestivation and organ regeneration. The sea cucumber does not possess a reorganized Hox cluster as previously assumed for all echinoderms, and the spatial expression of Hox7 and Hox11/13b potentially guides the embryo-to-larva axial transformation. Contrary to the typical production of lanosterol in animal cholesterol synthesis, the oxidosqualene cyclase of sea cucumber produces parkeol for saponin synthesis and has "plant-like" motifs suggestive of convergent evolution. The transcriptional factors Klf2 and Egr1 are identified as key regulators of aestivation, probably exerting their effects through a clock gene-controlled process. Intestinal hypometabolism during aestivation is driven by the DNA hypermethylation of various metabolic gene pathways, whereas the transcriptional network of intestine regeneration involves diverse signaling pathways, including Wnt, Hippo and FGF. Decoding the sea cucumber genome provides a new avenue for an in-depth understanding of the extraordinary features of sea cucumbers and other echinoderms.

Osbourn A. E., Boutanaev A. M. (2018)

Multigenome analysis implicates miniature inverted-repeat transposable elements (MITEs) in metabolic diversification in eudicots

Proceedings of the National Academy of Sciences of the United States of America

Publisher's version: 10.1073/pnas.1721318115

ID: 59291

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Recently discovered biosynthetic gene clusters in plants are a striking example of the nonrandom complex structure of eukaryotic genomes. The mechanisms underpinning the formation of these clustered pathways are not understood. Here we carry out a systematic analysis of transposable elements associated with clustered terpene biosynthetic genes in plant genomes, and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Our analyses provide insights into potential mechanisms of cluster assembly. They also shed light on the emergence of a “block” mechanism for the foundation of new terpene clusters in the eudicots in which microsyntenic blocks of terpene synthase and cytochrome P450 gene pairs duplicate, providing templates for the evolution of new pathways.Plants produce a plethora of natural products, including many drugs. It has recently emerged that the genes encoding different natural product pathways may be organized as biosynthetic gene clusters in plant genomes, with >30 examples reported so far. Despite superficial similarities with microbes, these clusters have not arisen by horizontal gene transfer, but rather by gene duplication, neofunctionalization, and relocation via unknown mechanisms. Previously we reported that two Arabidopsis thaliana biosynthetic gene clusters are located in regions of the genome that are significantly enriched in transposable elements (TEs). Other plant biosynthetic gene clusters also harbor abundant TEs. TEs can mediate genomic rearrangement by providing homologous sequences that enable illegitimate recombination and gene relocation. Thus, TE-mediated recombination may contribute to plant biosynthetic gene cluster formation. TEs may also facilitate establishment of regulons. However, a systematic analysis of the TEs associated with plant biosynthetic gene clusters has not been carried out. Here we investigate the TEs associated with clustered terpene biosynthetic genes in multiple plant genomes and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Through investigation of the newly sequenced Amborella trichopoda, Aquilegia coerulea, and Kalanchoe fedtschenkoi genomes, we further show that the “block” mechanism of founding of biosynthetic gene clusters through duplication and diversification of pairs of terpene synthase and cytochrome P450 genes that is prevalent in the eudicots arose around 90–130 million years ago, after the appearance of the basal eudicots and before the emergence of the superrosid clade.

Xue Z., Tan Z., Huang A., Zhou Y., Sun J., Wang X., Thimmappa R. B., Stephenson M. J., Osbourn A., Qi X. (2018)

Identification of key amino acid residues determining product specificity of 2,3-oxidosqualene cyclase in Oryza species.

New Phytologist

Publisher's version: 10.1111/nph.15080

ID: 58298

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Triterpene synthases, also known as 2,3-oxidosqualene cyclases (OSCs), synthesize diverse triterpene skeletons that form the basis of an array of functionally divergent steroids and triterpenoids. Tetracyclic and pentacyclic triterpene skeletons are synthesized via protosteryl and dammarenyl cations, respectively. The mechanism of conversion between two scaffolds is not well understood. Here, we report a promiscuous OSC from rice (Oryza sativa) (OsOS) that synthesizes a novel pentacyclic triterpene orysatinol as its main product. The OsOS gene is widely distributed in indica subspecies of cultivated rice and in wild rice accessions. Previously, we have characterized a different OSC, OsPS, a tetracyclic parkeol synthase found in japonica subspecies. Phylogenetic and protein structural analyses identified three key amino acid residues (#732, #365, #124) amongst 46 polymorphic sites that determine functional conversion between OsPS and OsOS, specifically, the chair-semi(chair)-chair and chair-boat-chair interconversions. The different orientation of a fourth amino acid residue Y257 was shown to be important for functional conversion The discovery of orysatinol unlocks a new path to triterpene diversity in nature. Our findings also reveal mechanistic insights into the cyclization of oxidosqualene into tetra- and pentacyclic skeletons, and provide a new strategy to identify key residues determining OSC specificity.

Goossens A., Osbourn A., Michoux F., Bak S. (2018)

Triterpene Messages from the EU-FP7 Project TriForC.

Trends in Plant Science

Publisher's version: 10.1016/j.tplants.2018.02.002

ID: 58375

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TriForC is an innovative EU-funded collaborative project that has established an integrative pipeline for the exploitation of plant triterpenes for commercialization in agriculture and pharmacology. We discuss the main outcomes of TriForC and reflect on its potential long-term impact and on the importance of EU projects for science, industry, and society.

Huang A. C., Hong Y. J., Bond A. D., Tantillo D. J., Osbourn A. (2017)

Diverged Plant Terpene Synthases Reroute the Carbocation Cyclization Path towards the Formation of Unprecedented 6/11/5 and 6/6/7/5 Sesterterpene Scaffolds.

Angewandte Chemie (International ed. in English)

Publisher's version: 10.1002/anie.201711444

ID: 57911

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Sesterterpenoids are a relatively rare class of plant terpenes. Sesterterpene synthase (STS)-mediated cyclization of the linear C25 isoprenoid precursor geranylfarnesyl diphosphate (GFPP) defines sesterterpene scaffolds. So far only a very limited number of STSs have been characterized. The discovery of three new plant STSs is reported that produce a suite of sesterterpenes with unprecedented 6/11/5 and 6/6/7/5 fused ring systems when transiently co-expressed with a GFPP synthase in Nicotiana benthamiana. Structural elucidation, feeding experiments, and quantum chemical calculations suggest that these STSs catalyze an unusual cyclization path involving reprotonation, intramolecular 1,6 proton transfer, and concerted but asynchronous bicyclization events. The cyclization is diverted from those catalyzed by the characterized plant STSs by forming unified 15/5 bicyclic sesterterpene intermediates. Mutagenesis further revealed a conserved amino acid residue implicated in reprotonation

Boobier S., Osbourn A., Mitchell J. B. O. (2017)

Can human experts predict solubility better than computers?

Journal of cheminformatics (9) 63

Publisher's version: 10.1186/s13321-017-0250-y

ID: 57890

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In this study, we design and carry out a survey, asking human experts to predict the aqueous solubility of druglike organic compounds. We investigate whether these experts, drawn largely from the pharmaceutical industry and academia, can match or exceed the predictive power of algorithms. Alongside this, we implement 10 typical machine learning algorithms on the same dataset. The best algorithm, a variety of neural network known as a multi-layer perceptron, gave an RMSE of 0.985 log S units and an R2 of 0.706. We would not have predicted the relative success of this particular algorithm in advance. We found that the best individual human predictor generated an almost identical prediction quality with an RMSE of 0.942 log S units and an R2 of 0.723. The collection of algorithms contained a higher proportion of reasonably good predictors, nine out of ten compared with around half of the humans. We found that, for either humans or algorithms, combining individual predictions into a consensus predictor by taking their median generated excellent predictivity. While our consensus human predictor achieved very slightly better headline figures on various statistical measures, the difference between it and the consensus machine learning predictor was both small and statistically insignificant. We conclude that human experts can predict the aqueous solubility of druglike molecules essentially equally well as machine learning algorithms. We find that, for either humans or algorithms, combining individual predictions into a consensus predictor by taking their median is a powerful way of benefitting from the wisdom of crowds.

Huang A. C., Kautsar S. A., Hong Y. J., Medema M. H., Bond A. D., Tantillo D. J., Osbourn A. (2017)

Unearthing a sesterterpene biosynthetic repertoire in the Brassicaceae through genome mining reveals convergent evolution.

Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A. 2017 Jul 3. pii: 201705567. doi: 10.1073/pnas.1705567114. ) Epub ahead of print

Publisher's version: 10.1073/pnas.1705567114

ID: 56890

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Sesterterpenoids are a rare terpene class harboring untapped chemodiversity and bioactivities. Their structural diversity originates primarily from the scaffold-generating sesterterpene synthases (STSs). In fungi, all six known STSs are bifunctional, containing C-terminal trans-prenyltransferase (PT) and N-terminal terpene synthase (TPS) domains. In plants, two colocalized PT and TPS gene pairs from Arabidopsis thaliana were recently reported to synthesize sesterterpenes. However, the landscape of PT and TPS genes in plant genomes is unclear. Here, using a customized algorithm for systematically searching plant genomes, we reveal a suite of physically colocalized pairs of PT and TPS genes for the biosynthesis of a large sesterterpene repertoire in the wider Brassicaceae. Transient expression of seven TPSs from A. thaliana, Capsella rubella, and Brassica oleracea in Nicotiana benthamiana yielded fungal-type sesterterpenes with tri-, tetra-, and pentacyclic scaffolds, and notably (-)-ent-quiannulatene, an enantiomer of the fungal metabolite (+)-quiannulatene. Protein and structural modeling analysis identified an amino acid site implicated in structural diversification. Mutation of this site in one STS (AtTPS19) resulted in premature termination of carbocation intermediates and accumulation of bi-, tri-, and tetracyclic sesterterpenes, revealing the cyclization path for the pentacyclic sesterterpene (-)-retigeranin B. These structural and mechanistic insights, together with phylogenetic analysis, suggest convergent evolution of plant and fungal STSs, and also indicate that the colocalized PT-TPS gene pairs in the Brassicaceae may have originated from a common ancestral gene pair present before speciation. Our findings further provide opportunities for rapid discovery and production of sesterterpenes through metabolic and protein engineering.

Reed J., Stephenson M. J., Miettinen K., Brouwer B., Leveau A., Brett P., Goss R. J. M., Goossens A., O'Connell M. A., Osbourn A. (2017)

A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules.

Metabolic Engineering (42) 185-193

Publisher's version: 10.1016/j.ymben.2017.06.012

ID: 56918

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Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines.

Osbourn A., Rant J., McLean T., Hutchings M., Truman A., Wilkinson B. (2017)

SAW antibiotics

ID: 58149

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This book showcases research from the NRP on antibiotics and disease control.  In the work presented here, scientists from the NRP collaborated with artists, writers and teachers to explore their science using the Science, Art and Writing (SAW) initiative as a vehicle for engagement (   SAW uses themes and images from science as the starting point for scientific experimentation, art and creative writing, and in doing so stimulates creativity, scientific curiosity and discussion.

Owen C., Patron N. J., Huang A., Osbourn A. (2017)

Harnessing plant metabolic diversity.

Current Opinion in Chemical Biology (40) 24-30

Publisher's version: 10.1016/j.cbpa.2017.04.015

ID: 56498

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Advances in DNA sequencing and synthesis technologies in the twenty-first century are now making it possible to build large-scale pipelines for engineering plant natural product pathways into heterologous production species using synthetic biology approaches. The ability to decode the chemical potential of plants by sequencing their transcriptomes and/or genomes and to then use this information as an instruction manual to make drugs and other high-value chemicals is opening up new routes to harness the vast chemical diversity of the Plant Kingdom. Here we describe recent progress in methods for pathway discovery, DNA synthesis and assembly, and expression of engineered pathways in heterologous hosts. We also highlight the importance of standardization and the challenges associated with dataset integration in the drive to build a systematic framework for effective harnessing of plant metabolic diversity.

Kautsar S. A., Suarez Duran H. G., Blin K., Osbourn A., Medema M. H. (2017)

plantiSMASH: automated identification, annotation and expression analysis of plant biosynthetic gene clusters.

Nucleic Acids Research (epub ) epub

Publisher's version: 10.1093/nar/gkx305

ID: 56210

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Plant specialized metabolites are chemically highly diverse, play key roles in host-microbe interactions, have important nutritional value in crops and are frequently applied as medicines. It has recently become clear that plant biosynthetic pathway-encoding genes are sometimes densely clustered in specific genomic loci: biosynthetic gene clusters (BGCs). Here, we introduce plantiSMASH, a versatile online analysis platform that automates the identification of candidate plant BGCs. Moreover, it allows integration of transcriptomic data to prioritize candidate BGCs based on the coexpression patterns of predicted biosynthetic enzyme-coding genes, and facilitates comparative genomic analysis to study the evolutionary conservation of each cluster. Applied on 48 high-quality plant genomes, plantiSMASH identifies a rich diversity of candidate plant BGCs. These results will guide further experimental exploration of the nature and dynamics of gene clustering in plant metabolism. Moreover, spurred by the continuing decrease in costs of plant genome sequencing, they will allow genome mining technologies to be applied to plant natural product discovery. The plantiSMASH web server, precalculated results and source code are freely available from

Zhou Y., Ma Y., Zeng J., Duan L., Xue X., Wang H., Lin T., Liu Z., Zeng K., Zhong Y., Zhang S., Hu Q., Liu M., Zhang H., Reed J., Moses T., Liu X., Huang P., Qing Z., Liu X., Tu P., Kuang H., Zhang Z., Osbourn A., Ro D. K., Shang Y., Huang S. (2016)

Convergence and divergence of bitterness biosynthesis and regulation in Cucurbitaceae.

Nature plants (2) 16183

Publisher's version: 10.1038/nplants.2016.183

ID: 55347

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Differentiation of secondary metabolite profiles in closely related plant species provides clues for unravelling biosynthetic pathways and regulatory circuits, an area that is still underinvestigated. Cucurbitacins, a group of bitter and highly oxygenated tetracyclic triterpenes, are mainly produced by the plant family Cucurbitaceae. These compounds have similar structures, but differ in their antitumour activities and ecophysiological roles. By comparative analyses of the genomes of cucumber, melon and watermelon, we uncovered conserved syntenic loci encoding metabolic genes for distinct cucurbitacins. Characterization of the cytochrome P450s (CYPs) identified from these loci enabled us to unveil a novel multi-oxidation CYP for the tailoring of the cucurbitacin core skeleton as well as two other CYPs responsible for the key structural variations among cucurbitacins C, B and E. We also discovered a syntenic gene cluster of transcription factors that regulates the tissue-specific biosynthesis of cucurbitacins and may confer the loss of bitterness phenotypes associated with convergent domestication of wild cucurbits. This study illustrates the potential to exploit comparative genomics to identify enzymes and transcription factors that control the biosynthesis of structurally related yet unique natural products.

Salmon M., Thimmappa R., Minto R., Melton R., Hughes R., O'Maille P., Hemmings A. M., Osbourn A. (2016)

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases.

Proceedings of the National Academy of Sciences of the United States of America (113(30)) E4407-E4414

Publisher's version: 10.1073/pnas.1605509113

ID: 53714

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Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.


The last decade has seen the first major discoveries regarding the genomic basis of plant natural product biosynthetic pathways. Four key computationally driven strategies have been developed to identify such pathways, which make use of physical clustering, co-expression, evolutionary co-occurrence and epigenomic co-regulation of the genes involved in producing a plant natural product. Here, we discuss how these approaches can be used for the discovery of plant biosynthetic pathways encoded by both chromosomally clustered and non-clustered genes. Additionally, we will discuss opportunities to prioritize plant gene clusters for experimental characterization, and end with a forward-looking perspective on how synthetic biology technologies will allow effective functional reconstitution of candidate pathways using a variety of genetic systems

Nuetzmann H. W., Huang A., Osbourn A. (2016)

Tansley Review: Plant metabolic clusters - from genetics to genomics

New Phytologist (211) 771789

Publisher's version: 10.1111/nph.13981

ID: 53072

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Plant natural products are of great value for agriculture, medicine and a wide range of other industrial applications. The discovery of new plant natural product pathways is currently being revolutionized by two key developments. First, breakthroughs in sequencing technology and reduced cost of sequencing are accelerating the ability to find enzymes and pathways for the biosynthesis of new natural products by identifying the underlying genes. Second, there are now multiple examples in which the genes encoding certain natural product pathways have been found to be grouped together in biosynthetic gene clusters within plant genomes. These advances are now making it possible to develop strategies for systematically mining multiple plant genomes for the discovery of new enzymes, pathways and chemistries. Increased knowledge of the features of plant metabolic gene clusters – architecture, regulation and assembly – will be instrumental in expediting natural product discovery. This review summarizes progress in this area.

Yu N., Nützmann H. W., MacDonald J. T., Moore B., Field B., Berriri S., Trick M., Rosser S. J., Kumar S. V., Freemont P. S., Osbourn A. (2016)

Delineation of metabolic gene clusters in plant genomes by chromatin signatures.

Nucleic Acids Research (44) 1-11

Publisher's version: 10.1093/nar/gkw100

ID: 52626

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Plants are a tremendous source of diverse chemicals, including many natural product-derived drugs. It has recently become apparent that the genes for the biosynthesis of numerous different types of plant natural products are organized as metabolic gene clusters, thereby unveiling a highly unusual form of plant genome architecture and offering novel avenues for discovery and exploitation of plant specialized metabolism. Here we show that these clustered pathways are characterized by distinct chromatin signatures of histone 3 lysine trimethylation (H3K27me3) and histone 2 variant H2A.Z, associated with cluster repression and activation, respectively, and represent discrete windows of co-regulation in the genome. We further demonstrate that knowledge of these chromatin signatures along with chromatin mutants can be used to mine genomes for cluster discovery. The roles of H3K27me3 and H2A.Z in repression and activation of single genes in plants are well known. However, our discovery of highly localized operon-like co-regulated regions of chromatin modification is unprecedented in plants. Our findings raise intriguing parallels with groups of physically linked multi-gene complexes in animals and with clustered pathways for specialized metabolism in filamentous fungi.

Osbourn A., Morgan J. (2016)

Editorial overview: Plant biotechnology

Current Opinion in Biotechnology (37) 153154

Publisher's version: 10.1016/j.copbio.2015.12.006

ID: 52572

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In summary, we believe that the articles in this issue give timely and inspiring insights into advances, challenges and opportunities in some of the key aspects of plant biotechnology. Plants are globally cultivated at extremely low cost, harvested on the giga-tonne scale, and routinely used to produce the widest range of products from fibers, wood, oils, sugar, fine chemicals, drugs to food. They represent an enormous and largely untapped source of enzymes and biochemicals for food, health, and industrial biotechnology applications. They can also be used as workhorses for the heterologous production of vaccines and other high value products. The continued development of ever more sophisticated tools and technologies for investigating, engineering, and improving plants coupled with the array of potential applications of plant biotechnology makes this a very exciting field to be in.

Osbourn A., Morgan J. (2016)

Editorial overview: Plant biotechnology

Current Opinion in Biotechnology (37) 153-154

Publisher's version: 10.1016/j.copbio.2015.12.006

ID: 52432

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In summary, we believe that the articles in this issue give timely and inspiring insights into advances, challenges and opportunities in some of the key aspects of plant biotechnology. Plants are globally cultivated at extremely low cost, harvested on the giga-tonne scale, and routinely used to produce the widest range of products from fibers, wood, oils, sugar, fine chemicals, drugs to food. They represent an enormous and largely untapped source of enzymes and biochemicals for food, health, and industrial biotechnology applications. They can also be used as workhorses for the heterologous production of vaccines and other high value products. The continued development of ever more sophisticated tools and technologies for investigating, engineering, and improving plants coupled with the array of potential applications of plant biotechnology makes this a very exciting field to be in.

Alagna F., Geu-Flores F., Kries H., Panara F., Baldoni L., O'Connor S. E., Osbourn A. (2015)

Identification and characterization of the iridoid synthase involved in oleuropein biosynthesis in olive (Olea europaea) fruits.

Journal of Biological Chemistry (291) 55425554

Publisher's version: 10.1074/jbc.M115.701276

ID: 52575

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The secoiridoids are the main class of specialized metabolites present in olive (Olea europaea L.) fruit. In particular, the secoiridoid oleuropein strongly influences olive oil quality due to its bitterness, which is a desirable trait. In addition, oleuropein possesses a wide range of pharmacological properties, including antioxidant, antiinflammatory, and anti-cancer activities. In accordance, obtaining high-oleuropein varieties is a main goal of molecular breeding programs. Here we use a transcriptomic approach to identify candidate genes belonging to the secoiridoid pathway in olive. From these candidates, we have functionally characterized the olive homologue of iridoid synthase (OeISY), an unusual terpene cyclase that couples an NAD(P)H-dependent 1,4-reduction step with a subsequent cyclization, and we provide evidence that OeISY likely generates the monoterpene scaffold of oleuropein in olive fruits. OeISY, the first pathway gene characterised for this type of secoiridoid, is a potential target for breeding programs in a high value secoiridoid-accumulating species.

Osbourn A. (2015)

Anne Osbourn.

New Phytologist (208) 23-5

Publisher's version: 10.1111/nph.13616

ID: 51848

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Anne Osbourn is a Project Leader at the John Innes Centre and Director of the Norwich Research Park Industrial Biotechnology and Bioenergy Alliance. She is also a Trustee of the New Phytologist Trust and an Editor of New Phytologist. Her research focuses on plant-derived natural products – function, synthesis, mechanisms of metabolic diversification and metabolic engineering. An important advance from the Osbourn laboratory has been the discovery that genes for specialized metabolic pathways are organized in ‘operon-like’ clusters in plant genomes, a finding that has opened up new opportunities for elucidation of new pathways and chemistries through genome mining. Anne has developed and coordinates the Science, Art and Writing (SAW) Initiative, a cross-curricular science education outreach programme (

Patron N. J., Orzaez D., Marillonnet S., Warzecha H., Matthewman C., Youles M., Raitskin O., Leveau A., Farré G., Rogers C., Smith A., Hibberd J., Webb A. A., Locke J., Schornack S., Ajioka J., Baulcombe D. C., Zipfel C., Kamoun S., Jones J. D., Kuhn H., Robatzek S., Van Esse H. P., Sanders D., Oldroyd G., Martin C., Field R., O'Connor S., Fox S., Wulff B., Miller B., Breakspear A., Radhakrishnan G., Delaux P. M., Loqué D., Granell A., Tissier A., Shih P., Brutnell T. P., Quick W. P., Rischer H., Fraser P. D., Aharoni A., Raines C., South P. F., Ané J. M., Hamberger B. R., Langdale J., Stougaard J., Bouwmeester H., Udvardi M., Murray J. A., Ntoukakis V., Schäfer P., Denby K., Edwards K. J., Osbourn A., Haseloff J. (2015)

Standards for plant synthetic biology: a common syntax for exchange of DNA parts.

New Phytologist (208) 13-9

Publisher's version: 10.1111/nph.13532

ID: 55372

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Inventors in the field of mechanical and electronic engineering can access multitudes of components and, thanks to standardization, parts from different manufacturers can be used in combination with each other. The introduction of BioBrick standards for the assembly of characterized DNA sequences was a landmark in microbial engineering, shaping the field of synthetic biology. Here, we describe a standard for Type IIS restriction endonuclease-mediated assembly, defining a common syntax of 12 fusion sites to enable the facile assembly of eukaryotic transcriptional units. This standard has been developed and agreed by representatives and leaders of the international plant science and synthetic biology communities, including inventors, developers and adopters of Type IIS cloning methods. Our vision is of an extensive catalogue of standardized, characterized DNA parts that will accelerate plant bioengineering.

Medema M. H., Kottmann R., Yilmaz P., Cummings M., Biggins J. B., Blin K., de Bruijn I., Chooi Y. H., Claesen J., Coates R. C., Cruz-Morales P., Duddela S., Düsterhus S., Edwards D. J., Fewer D. P., Garg N., Geiger C., Gomez-Escribano J. P., Greule A., Hadjithomas M., Haines A. S., Helfrich E. J., Hillwig M. L., Ishida K., Jones A. C., Jones C. S., Jungmann K., Kegler C., Kim H. U., Kötter P., Krug D., Masschelein J., Melnik A. V., Mantovani S. M., Monroe E. A., Moore M., Moss N., Nützmann H. W., Pan G., Pati A., Petras D., Reen F. J., Rosconi F., Rui Z., Tian Z., Tobias N. J., Tsunematsu Y., Wiemann P., Wyckoff E., Yan X., Yim G., Yu F., Xie Y., Aigle B., Apel A. K., Balibar C. J., Balskus E. P., Barona-Gómez F., Bechthold A., Bode H. B., Borriss R., Brady S. F., Brakhage A. A., Caffrey P., Cheng Y. Q., Clardy J., Cox R. J., Donadio S., Donia M. S., van der Donk W. A., Dorrestein P. C., Doyle S., Driessen A. J., Ehling-Schulz M., Entian K. D., Fischbach M. A., Gerwick L., Gerwick W. H., Gross H., Gust B., Hertweck C., Höfte M., Jensen S. E., Ju J., Katz L., Kaysser L., Klassen J. L., Keller N. P., Kormanec J., Kuipers O. P., Kuzuyama T., Kyrpides N. C., Kwon H. J., Lautru S., Lavigne R., Lee C. Y., Linquan B., Liu X., Liu W., Luzhetskyy A., Mahmud T., Mast Y., Méndez C., Metsä-Ketelä M., Micklefield J., Mitchell D. A., Moore B. S., Moreira L. M., Müller R., Neilan B. A., Nett M., Nielsen J., O'Gara F., Oikawa H., Osbourn A., Osburne M. S., Ostash B., Payne S. M., Pernodet J. L., Petricek M., Piel J., Ploux O., Raaijmakers J. M., Salas J. A., Schmitt E. K., Scott B., Seipke R. F., Shen B., Sherman D. H., Sivonen K., Smanski M. J., Sosio M., Stegmann E., Süssmuth R. D., Tahlan K., Thomas C. M., Tang Y., Truman A. W., Viaud M., Walton J. D., Walsh C. T., Weber T., van Wezel G. P., Wilkinson B., Willey J. M., Wohlleben W., Wright G. D., Ziemert N., Zhang C., Zotchev S. B., Breitling R., Takano E., Glöckner F. O. (2015)

Minimum Information about a Biosynthetic Gene cluster

Nature Chemical Biology (11) 625-31

Publisher's version: 10.1038/nchembio.1890

ID: 51847

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A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters.  Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit.  To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

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