Birger Møller

• Dr.Sc.
• Professor (Full) at University of Copenhagen

Cytochrome P450s of the CYP79 family catalyze two N‐hydroxylation reactions, converting a selected number of amino acids into the corresponding oximes. The sorghum genome ( Sorghum bicolor ) harbours nine CYP79A encoding genes, and here sequence comparisons of the CYP79As along with their substrate recognition sites (SRSs) are provided. The substra...

Angraecum sesquipedale, also known as Darwin’s orchid, possesses an exceptionally long nectar spur. Charles Darwin predicted the orchid to be pollinated by a hawkmoth with a correspondingly long proboscis, later identified as Xanthopan praedicta. In this plant-pollinator interaction, the A. sesquipedale flower emits a complex blend of scent compoun...

Oximes are unrecognized chameleons in general and specialized plant metabolism. E- and Z-p-hydroxyphenylacetaldehyde oxime are key intermediates in the biosynthesis of the cyanogenic glucoside dhurrin produced in sorghum. Nevertheless, none of the geometrical oxime isomers accumulate in the plant. Herein, we report a convenient route to the chemica...

Cytochrome P450 monooxygenases of the CYP79 family catalyze conversion of specific amino acids into oximes feeding into a variety of metabolic plant pathways. Here we present an extensive phylogenetic tree of the CYP79 family built on carefully curated sequences collected across the entire plant kingdom. Based on a monophyletic origin of the P450s,...

Barley produces several specialized metabolites, including five α‐, β‐, and γ‐hydroxynitrile glucosides (HNGs). In malting barley, presence of the α‐HNG epiheterodendrin gives rise to undesired formation of ethyl carbamate in the beverage production, especially after distilling. Metabolite‐GWAS identified QTLs and underlying gene candidates possibl...

In this study, an extract of the leaves of Eremophila clarkei Oldfield & F.Muell. showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC50 value of 33.0 μg/mL. The extract was therefore investigated by high-resolution PTP1B inhibition profiling to pinpoint the constituents responsible for the activity. Subsequent isolation an...

Obesity is a major health risk still lacking effective pharmacological treatment. A potent anti-obesity agent, celastrol, has been identified in the roots of Tripterygium wilfordii. However, an efficient synthetic method is required to better explore its biological utility. Here we elucidate the 11 missing steps for the celastrol biosynthetic route...

Extracts of Eremophila phyllopoda subsp. phyllopoda showed α-glucosidase and PTP1B inhibitory activity with IC50 values of 19.6 and 13.6 μg/mL, respectively. High-resolution α-glucosidase/PTP1B/radical scavenging profiling was performed to establish a triple high-resolution inhibition profile that allowed direct pinpointing of the constituents resp...

Discovery of sustainable and benign-by-design drugs to combat emerging health pandemics calls for new analytical technologies to explore the chemical and pharmacological properties of Nature's unique chemical space. Here, we present a new analytical technology workflow, polypharmacology-labeled molecular networking (PLMN), where merged positive and...

The economic and ecologically important genus Eucalyptus is rich in structurally diverse specialized metabolites. While some specialized metabolite classes are highly prevalent across the genus, the cyanogenic glucoside prunasin is only produced by c. 3% of species. To investigate the evolutionary mechanisms behind prunasin biosynthesis in Eucalypt...

Grain size and weight are two of the most important determinants of crop yield. Key genes associated with the grain size and weight have been identified in major crops. However, studies on the genetic basis of the grain size and weight related genes in wild Sorghum are limited. In this study, we analysed the variation of grain size related genes us...

The ginkgo tree ( Ginkgo biloba ) is considered a living fossil due to its 200 million year’s history under morphological stasis. Its resilience is partly attributed to its unique set of specialized metabolites, in particular, ginkgolides and bilobalide, which are chemically complex terpene trilactones. Here, we use a gene cluster-guided mining app...

1 The plant genus Eremophila is endemic to Australia and widespread in arid regions. Root bark extract of Eremophila longifolia (R.Br.) F.Muell. (Scrophulariaceae) was investigated by LC-PDA-HRMS, and dereplication suggested the presence of a series of diterpenoids. Using a combination of preparative- and analytical-scale HPLC separation as well as...

Improved agricultural and industrial production organisms are required to meet the future global food demands and minimize the effects of climate change. A new resource for crop and microbe improvement, designated FIND-IT (Fast Identification of Nucleotide variants by droplet DigITal PCR), provides ultrafast identification and isolation of predeter...

The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosyn...

In a cross‐continental research initiative including researchers in Australia and Denmark and based on joint external funding by a three year grant from the Novo Nordisk Foundation, we have used DNA sequencing, extensive chemical profiling and molecular networking analyses across the entire Eremophila genus to provide new knowledge on the presence...

Eremophila (Scrophulariaceae) is a genus of Australian desert plants, which have been used by Australian Aboriginal people for various medicinal purposes. Crude extracts of the leaf resin of Eremophila glabra (R.Br.) Ostenf. showed α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC 50 values of 19.3 ± 1.2 μg/mL an...

Using synthetic biology, it is now time to expand the biosynthetic repertoire of plants and microalgae by utilizing the chloroplast to augment the production of desired high-value compounds and of oil-, carbohydrate-, or protein-enriched biomass based on direct harvesting of solar energy and the consumption of CO2. Multistream product lines based o...

Crude extract of Eremophila spathulata leaves was investigated by semi-preparative scale high-performance liquid chromatography (HPLC), analytical scale HPLC, and hyphenated high-performance liquid chromatography-photodiode array-high-resolution mass spectrometry-nuclear magnetic resonance (HPLC-PDA-HRMS-SPE-NMR), which afforded seven previously un...

Main conclusion Australian native species of sorghum contain negligible amounts of dhurrin in their leaves and the cyanogenesis process is regulated differently under water-stress in comparison to domesticated sorghum species. Abstract Cyanogenesis in forage sorghum is a major concern in agriculture as the leaves of domesticated sorghum are potent...

Domestication has resulted in a loss of genetic diversity in our major food crops, leading to susceptibility to biotic and abiotic stresses linked with climate change. Crop wild relatives (CWR) may provide a source of novel genes potentially important for re-gaining climate resilience. Sorghum bicolor is an important cereal crop with wild relatives...

Main conclusion Developmental and organ-specific expression of genes in dhurrin biosynthesis, bio-activation, and recycling offers dynamic metabolic responses optimizing growth and defence responses in Sorghum . Abstract Plant defence models evaluate the costs and benefits of resource investments at different stages in the life cycle. Poor underst...

Sorghum [Sorghum bicolor (L.) Moench] is an important food crop with a diverse gene pool residing in its wild relatives. A total of 15 sorghum accessions from the unexploited wild gene pool of the Sorghum genus, representing the five subgenera, were sequenced, and the complete chloroplast genomes and 99 common single‐copy concatenated nuclear genes...

Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic...

The superfamily of cytochrome P450 (CYP) enzymes plays key roles in plant evolution and metabolic diversification. This review provides a status on the CYP landscape within green algae and land plants. The 11 conserved CYP clans known from vascular plants are all present in green algae and several green algae-specific clans are recognized. Clan 71,...

This chapter illustrates how metabolic engineering of photosynthetic organisms offers science-based approaches enabling humanity to address some of the global challenges we are facing while facilitating the transition from fossil fuel-dependent production to a biobased society, i.e. moving from the Anthropocene Era to the Planthropocene Era. Plants...

Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cyto-chromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and nat...

Domestication has narrowed the genetic diversity found in crop wild relatives, potentially reducing plasticity to cope with a changing climate. The tissues of domesticated sorghum (Sorghum bicolor), especially in younger plants, are cyanogenic and potentially toxic. Species of wild sorghum produce lower levels of the cyanogenic glucoside (CNglc) dh...

Plant natural products encompass an enormous chemical diversity bearing witness to great molecular innovation that occured throughout land plant evolution. Cytochrome P450 monooxygenases (CYPs) catalyze a wide variety of monooxygenation reactions essential to the metabolic repertoire of plants natural products. Ferns constitute the second largest g...

Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic...

Phytocannabinoids are a group of plant-derived metabolites that display a wide range of psychoactive as well as health-promoting effects. The production of pharmaceutically relevant cannabinoids relies on extraction and purification from cannabis (Cannabis sativa) plants yielding the major constituents, Δ9-tetrahydrocannabinol and cannabidiol. Hete...

An insufficient vocabulary and lack of a proper molecular grammar tends to simplify the exquisite organization of the cellular environment in which plant metabolism is orchestrated. Chaos at the cellular level would not have enabled plants to evolve as the chemists par excellence in nature. Certain molecules such as sugars, amino acids and organic...

A methylene chloride extract of Myoporum insulare R. Br. (Scrophulariaceae) root material was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. Subsequent analytical-scale separation of the crude extract afforded serrulatanes 1-9 of which 2 ((1R,11S,18R)-5,18-epoxyserrulat-3,14-dien-8,18-diol or myoporul...

Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natu...

Cyanogenic glycosides form part of a binary plant defense system that, upon catabolism, detonates a toxic hydrogen cyanide bomb. In seed plants, the initial step of cyanogenic glycoside biosynthesis—the conversion of an amino acid to the corresponding aldoxime—is catalyzed by a cytochrome P450 from the CYP79 family. An evolutionary conundrum arises...

Metabolic control is mediated by the dynamic assemblies and function of multiple redox enzymes. A key element in these assemblies, the P450 oxidoreductase (POR), donates electrons and selectively activates numerous (>50 in humans and >300 in plants) cytochromes P450 (CYPs) controlling metabolism of drugs, steroids and xenobiotics in humans and natu...

Lima bean, Phaseolus lunatus , is a crop legume that produces the cyanogenic glucosides linamarin and lotaustralin. In the legumes Lotus japonicus and Trifolium repens , the biosynthesis of these two α‐hydroxynitrile glucosides involves cytochrome P450 enzymes of the CYP79 and CYP736 families and a UDP‐glucosyltransferase. Here, we identify CYP79D7...

Lima bean, Phaseolus lunatus, is a crop legume that produces the cyanogenic gluco-sides linamarin and lotaustralin. In the legumes Lotus japonicus and Trifolium repens, the biosynthesis of these two α-hydroxynitrile glucosides involves cytochrome P450 enzymes of the CYP79 and CYP736 families and a UDP-glucosyltransferase. Here, we identify CYP79D71...

Phytocannabinoids are bioactive natural products found in some flowering plants, liverworts, and fungi that can be beneficial for the treatment of human ailments such as pain, anxiety, and cachexia. Targeted biosynthesis of cannabinoids with desirable properties requires identification of the underlying genes and their expression in a suitable hete...

Eucalypts (including Angophora, Corymbia, Eucalyptus) comprise a large and hyper-diverse group of ecologically important trees providing habitats for many forest dependent species. Eucalypts synthesize a plethora of specialized metabolites that moderate biotic and abiotic interactions. Until now, studies on eucalypt volatile organic compounds (VOCs...

Ten new branched-chain fatty acid (BCFA) dimers with a substituted cyclohexene structure, five new monomers, and two known monomers, (2E,4Z,6E)-5-(acetoxymethyl)tetradeca-2,4,6-trienoic acid and its 5-hydroxymethyl analogue, were identified in the leaf extract of Eremophila oppositifolia subsp. angustifolia using a combination of HPLC-PDA-HRMS-SPE-...

This study presents a level-1 identification of c-methyl-scyllo-inositol (mytilitol) in mussels and clams (Mytilus and Ruditapes spp., respectively) purchased in Denmark and Italy. For each sample, the hydrophilic extract of the soft tissue was analyzed by proton nuclear magnetic resonance (¹H-NMR) spectroscopy using a 600 MHz NMR spectrometer. A f...

Background: Eremophila R.Br. (Scrophulariaceae) is a diverse genus of plants with species distributed across semi-arid and arid Australia. It is an ecologically important genus that also holds cultural significance for many Indigenous Australians who traditionally use several species as sources of medicines. Structurally unusual diterpenoids, part...

Background: Celastrol is a promising anti-obesity agent that acts as a sensitizer of the protein hormone leptin. Despite its potent activity, a sustainable source of celastrol and celastrol derivatives for further pharmacological studies is lacking. Results: To elucidate the celastrol biosynthetic pathway and reconstruct it in Saccharomyces cere...

Covering: Up to 2019 Phenolic cross-links and phenolic inter-unit linkages result from the oxidative coupling of two hydroxycinnamates or two molecules of tyrosine. Free dimers of hydroxycinnamates, lignans, play important roles in plant defence. Cross-linking of bound phenolics in the plant cell wall affects cell expansion, wall strength, digestib...

In recent years, ionic liquids and deep eutectic solvents (DESs) have gained increasing attention due to their ability to extract and solubilize metabolites and biopolymers in quantities far beyond their solubility in oil and water. The hypothesis that naturally occurring metabolites are able to form a natural deep eutectic solvent (NADES), thereby...

Sorghum bicolor (L.) Moench produces the nitrogen-containing natural product dhurrin that provides chemical defense against herbivores and pathogens via the release of toxic hydrogen cyanide gas. Drought can increase dhurrin in shoot tissues to concentrations toxic to livestock. As dhurrin is also a remobilizable store of reduced nitrogen and plays...

Eremophila bignoniiflora is a shrub distributed throughout inland northern and eastern Australia, and it has been used in several medicinal applications by some Australian Aboriginal people. In our continued search for anti-diabetic constituents from natural resources, the crude ethyl acetate extract of E. bignoniiflora was found to have protein-ty...

Plants and cyanobacteria are promising heterologous hosts for metabolic engineering, and particularly suited for expression of cytochrome P450 (P450s), enzymes that catalyse key steps in biosynthetic pathways leading to valuable natural products such as alkaloids, terpenoids and phenylpropanoids. P450s are often difficult to express and require a m...

[Draft] Sorghum bicolor is an important cereal crop grown in arid and semi-arid regions. Despite its high drought tolerance, S. bicolor is susceptible to severe drought, leading to a reduction in grain yield and plant biomass. In the leaves, drought also promotes accumulation of the cyanogenic glucoside dhurrin that gives rise to hydrogen cyanide r...

Environmental stress reduces yield and quality in crop plants. Understanding these stresses is an essential enabler for mitigating breeding strategies and becomes more important as the frequency of extreme weather events increases due to climate change. This study analyses the response of barley (Hordeum vulgare L.) to a heat wave during grain fill...

How to make almonds palatable The domesticated almond tree has been feeding humans for millennia. Derivation from the wild, bitter, and toxic almond required loss of the cyanogenic diglucoside amygdalin. Sánchez-Pérez et al. sequenced the almond genome and analyzed the genomic region responsible for this shift. The key change turned out to be a poi...

Background Controlled turnover of proteins as mediated by the ubiquitin proteasome system (UPS) is an important element in plant defense against environmental and pathogen stresses. E3 ligases play a central role in subjecting proteins to hydrolysis by the UPS. Recently, it has been demonstrated that a specific class of E3 ligases termed the U-box...

Barley (Hordeum vulgare L.) produces five leucine-derived hydroxynitrile glucosides, potentially involved in alleviating pathogen and environmental stresses. These compounds include the cyanogenic glucoside epiheterodendrin. The biosynthetic genes are clustered. Total hydroxynitrile glucoside contents were previously shown to vary from zero to more...

Background: Forskolin is a high-value diterpenoid produced exclusively by the Lamiaceae plant Coleus forskohlii. Today forskolin is used pharmaceutically for its adenyl-cyclase activating properties. The limited availability of pure forskolin is currently hindering its full utilization, thus a new environmentally friendly, scalable and sustainable...

Covering: up to 2018Plants are sessile organisms. To compensate for not being able to escape when challenged by unfavorable growth conditions, pests or herbivores, plants have perfected their metabolic plasticity by having developed the capacity for on demand synthesis of a plethora of phytochemicals to specifically respond to the challenges arisin...

Almond (Prunus dulcis) is the principal Prunus species in which the consumed and thus commercially important part of the fruit is the kernel. As a result of continued selection, the vast majority of almonds have a non-bitter sweet kernel. However, in the field there are trees carrying bitter kernels, which are toxic to humans and, consequently, nee...

Cyanogenic glucosides are a class of specialized metabolites widespread in the plant kingdom. Cyanogenic glucosides are α-hydroxynitriles, and their hydrolysis releases toxic hydrogen cyanide providing an effective chemical defense against herbivores. Eucalyptus cladocalyx F. Muell. is a cyanogenic tree, allocating up to 20% of leaf nitrogen to the...

Abstract The natural red food colorants carmine (E120) and carminic acid are currently produced from scale insects. The access to raw material is limited and current production is sensitive to fluctuation in weather conditions. A cheaper and more stable supply is therefore desirable. Here we present the first proof-of-concept of heterologous microb...

Photosynthetic microalgae harbor enormous potential as light-driven green-cell factories for sustainable bio-production of a range of natural and heterologous products such as isoprenoids. Their capacity for photosynthesis and rapid low-input growth with (sun)light and CO2 is coupled to a robust metabolic architecture structured toward the generati...

Figure S1. In planta assays of class I enzymes VacTPS2 and VacTPS6 with a class II ent‐copalyl diphosphate synthase from Euphorbia peplus (EpTPS7). Figure S2. In planta assays of class I enzymes VacTPS2 and VacTPS6 with a class II labd‐13‐en‐8‐ol diphosphate synthase from Coleus forskohlii (CfTPS2). Figure S3. In planta assays of class I enzyme V...

Table S1. Genes used in the diTPS phylogenetic analysis. Table S2. Compounds reported in this paper and the method of identification. Table S3. Peregrinol (2) NMR data. Table S4. syn‐Copalol (4) NMR data. Table S5. Kolavenol NMR data. Table S6. 9,13‐Epoxy‐labd‐14‐ene (3a) NMR data. Table S7. Viteagnusin D (8) NMR data. Table S8. Labda‐13(16)...

This chapter reviews plants as chemical factories. We obtain a vast array of chemicals such as flavours, fragrances, and drugs from plants that are products of their metabolism. Plant metabolism can be classified as primary or secondary. The products of primary metabolism are crucial for the life processes, while those of secondary metabolism mostl...

The Australian plant Acacia ligulata has a number of traditional food and medicinal uses by Australian Aboriginal people, although no bioactive compounds have previously been isolated from this species. Bioassay-guided fractionation of an ethanolic extract of the mature pods of A. ligulata led to the isolation of the two new echinocystic acid trite...

Release of bud dormancy in perennial woody plants is a temperature-dependent process and thus flowering in these species is heavily affected by climate change. The lack of cold winters in temperate growing regions often results in reduced flowering and low fruit yields. This is likely to decrease the availability of fruits and nuts of the Prunus sp...

Sequences of the hydrogen cyanamide-responsive genes discussed in this study.

Pipeline used for RNA sequencing analysis of hydrogen cyanamide (HC)-treated and control flower buds of sweet cherry. CAS, beta-cyanoalanine synthase; DEGs, differentially expressed genes; GO, gene ontology.

List of differentially expressed genes in hydrogen cyanamide treated flower buds at 1, 3, and 6 dat including the corresponding enriched GO terms.

Three clusters of hydrogen-cyanamide responsive genes and the respective most enriched GO terms.

Results of two way ANOVA performed on phytohormone levels in sweet cherry flower buds treated with hydrogen cyanamide or with water as control at 0, 1, 3, 6, 8, 12, 15, and 18 dat.

List of differentially expressed genes in hydrogen cyanamide-treated flower buds independent of the development effect, including the most enriched GO terms.

List of DEGs that were co-expressed with CAS.