A5016963098- Plant biochemistry and biosynthesis
- Photosynthetic Processes and Mechanisms
- Natural product bioactivities and synthesis
- Algal biology and biofuel production
- Microbial Natural Products and Biosynthesis
- Plant-based Medicinal Research
- Microbial Metabolic Engineering and Bioproduction
- Transgenic Plants and Applications
- Natural Compounds in Disease Treatment
- Protist diversity and phylogeny
- Plant tissue culture and regeneration
- Microbial Community Ecology and Physiology
- Medicinal Plants and Bioactive Compounds
- Metabolomics and Mass Spectrometry Studies
- Microbial Metabolism and Applications
- Diatoms and Algae Research
- Plant Gene Expression Analysis
- Sesquiterpenes and Asteraceae Studies
- Antioxidant Activity and Oxidative Stress
- Bioactive Natural Diterpenoids Research
University of Copenhagen
2014-2024
Planta
2016-2023
University of California, Berkeley
2017-2020
Laboratoire de Biochimie
2017
Abstract Plant‐derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance high structural complexity limits broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations class I II synthases, 41 which are “new‐to‐nature”. Stereoselective over 50 skeletons was demonstrated, including variants novel enantiomeric or diastereomeric counterparts. Scalable...
Forskolin, a complex labdane diterpenoid found in the root of Coleus forskohlii (Lamiaceae), has received attention for its broad range pharmacological activities, yet biosynthesis not been elucidated. We detected forskolin cork C. specialized cell type containing characteristic structures with histochemical properties consistent oil bodies. Organelle purification and chemical analysis confirmed localization simplest diterpene precursor backbone, (13R) manoyl oxide, to The backbone is...
Forskolin is a high value diterpenoid with broad range of pharmaceutical applications, naturally found in root bark the plant Coleus forskohlii. Because its complex molecular structure, chemical synthesis forskolin not commercially attractive. Hence, labor and resource intensive extraction purification from C. forskohlii plants remains current source compound. We have engineered unicellular cyanobacterium Synechocystis sp. PCC 6803 to produce precursor 13R-manoyl oxide (13R-MO), paving way...
Forskolin is a unique structurally complex labdane-type diterpenoid used in the treatment of glaucoma and heart failure based on its activity as cyclic AMP booster. Commercial production forskolin relies exclusively extraction from only known natural source, plant Coleus forskohlii, which accumulates root cork. Here, we report discovery five cytochrome P450s two acetyltransferases catalyze cascade reactions converting precursor 13R-manoyl oxide into diverse array additional diterpenoids. A...
Significance Ingenol mebutate is a diterpene ester with highly complex macrocyclic structure that has been approved for the treatment of actinic keratosis, precondition skin cancer. The current production ingenol through plant extraction or chemical synthesis inefficient and costly. Here, we describe discovery biosynthetic route in Euphorbia lathyris L. (caper spurge) which regio-specific oxidation casbene followed by an unconventional cyclization to yield jolkinol C, probable key...
Summary Tripterygium wilfordii (Celastraceae) is a medicinal plant with anti‐inflammatory and immunosuppressive properties. Identification of vast array unusual sesquiterpenoids, diterpenoids triterpenoids in T. has spurred investigations their pharmacological The tri‐epoxide lactone triptolide was the first many identified, attracting interest due to spectrum bioactivities. To probe genetic underpinning diterpenoid diversity, an expansion class II diterpene synthase (di TPS ) family...
A key enzyme in light-harvesting pigment formation many algae stems from duplication of a gene involved photoprotection.
The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of abeo-abietane core structure present several other plant diterpenoids. In combination two CYPs CYP82D subfamily, four T. are shown to constitute...
Abstract Stramenopile algae contribute significantly to global primary productivity, and one class, Eustigmatophyceae, is increasingly studied for applications in high-value lipid production. Yet much about their basic biology remains unknown, including the nature of an enigmatic, pigmented globule found vegetative cells. Here, we present in-depth examination this “red body,” focusing on Nannochloropsis oceanica . During cell cycle, red body forms adjacent plastid, but unexpectedly it...
Plant terpenoids are known for their diversity, stereochemical complexity, and commercial interest as pharmaceuticals, food additives, cosmetics. Developing biotechnology approaches the production of these compounds in heterologous hosts can increase market availability, reduce cost, provide sustainable platforms. In this context, we aimed at producing antimicrobial diterpenoid isopimaric acid from Sitka spruce. Isopimaric is synthesized using geranylgeranyl diphosphate a precursor molecule...
The Mediterranean plant Thapsia garganica (dicot, Apiaceae), also known as deadly carrot, produces the highly toxic compound thapsigargin. This is a potent inhibitor of sarcoplasmic-endoplasmic reticulum Ca2+-ATPase calcium pump in mammals and industrial importance active moiety anticancer drug mipsagargin, currently clinical trials. Knowledge thapsigargin planta storage biosynthesis has been limited. Here, we present putative second step biosynthesis, by showing that cytochrome P450...
Abstract Plant‐derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance high structural complexity limits broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations class I II synthases, 41 which are “new‐to‐nature”. Stereoselective over 50 skeletons was demonstrated, including variants novel enantiomeric or diastereomeric counterparts. Scalable...
ABSTRACT Forskolin is a promising medicinal compound belonging to plethora of specialized plant metabolites that constitute rich source bioactive high-value compounds. A major obstacle for exploitation they often are produced in small amounts and plants difficult cultivate. This may result insufficient unreliable supply leading fluctuating high sales prices. Hence, substantial efforts resources have been invested developing sustainable reliable routes based on microbial cell factories. Here,...
Carminic acid is a C-glucosylated octaketide anthraquinone and the main constituent of natural dye carmine (E120), possessing unique coloring, stability, solubility properties. Despite being used since ancient times, longstanding efforts to elucidate its route biosynthesis have been unsuccessful. Herein, novel combination enzymes derived from plant (Aloe arborescens, Aa), bacterium (Streptomyces sp. R1128, St), an insect (Dactylopius coccus, Dc) that allows for anthraquinone, dcII, precursor...
Stramenopile algae have the potential to become light-driven photosynthetic biofactories of future, but transformation technologies required reach this goal remain sub-optimal. Nannochloropsis oceanica and Phaeodactylum tricornutum were used as experimental systems for electroporation-mediated transformation. Two approaches developed; 1) timed synchronized cells 2) addition saponins adjuvants. Transformation efficiency was increased ~8 times using N. cultures transformed in G2/M phase,...
Chlorophyll c is a key photosynthetic pigment that has been used historically to classify eukaryotic algae. Despite its importance in global productivity, the pathway for biosynthesis remained elusive. Here we define CHLOROPHYLL C SYNTHASE (CHLCS) discovered through investigation of dinoflagellate mutant deficient chlorophyll c. CHLCSs are proteins with a/b binding and 2-oxoglutarate-Fe(II) dioxygenase (2OGD) domains found peridinin-containing dinoflagellates; other c-containing algae...
Abstract Stramenopile algae contribute significantly to global primary productivity, and one class, Eustigmatophyceae, is increasingly studied for applications in high-value lipid production. Yet much about their basic biology remains unknown, including the nature of an enigmatic, pigmented globule found vegetative cells. Here, we present in-depth examination this “red body”, focusing on Nannochloropsis oceanica . During cell cycle, red body formed adjacent plastid, but unexpectedly it was...
The cover feature shows the partial assembly of a carmine puzzle. Co-expression genes from Aloe arborescens (top left), Streptomyces (bottom left) and Dactylopius coccus right) in Nicotiana benthamiana (background) lead to an accumulation dcII, glucosylated octaketide anthraquinone precursor popular natural colorant carminic acid right). More information can be found communication by B. Lindberg Møller, R. Kannangara et al. on page 1893 Issue 19, 2017 (DOI: 10.1002/cbic.201700331).