On the Role of Hydrogen Migrations in the Taxadiene System.

Taxa-4,11-diene is made by the taxa-4,11-diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI-MS fragmentation of taxa-4,11-diene.

Initial evaluation of 4-palmitoyloxy butyrate in whole blood as potential biomarker after γ-hydroxybutyric acid intake.

The problem of finding a suitable biomarker to widen the detection window of γ-hydroxybutyric acid (GHB) intake remains a challenge in forensic toxicology. Based on previously published results, the present study deals with the evaluation of a fatty acid ester of GHB (4-palmitoyloxy butyrate (GHB-Pal)) in whole blood as a potential biomarker to extend the detection window of GHB use e.g.

Biosynthesis of the Non-Canonical C Sesquiterpenoids Chlororaphen A and B from Pseudomonas Chlororaphis.

Chlororaphens A and B are structurally unique non-canonical C sesquiterpenoids from Pseudomonas chlororaphis that are made by two SAM-dependent methyltransferases and a type I terpene synthase. This study addresses the mechanism of their formation in isotopic labelling experiments and DFT calculations. The results demonstrate an astonishing complexity with distribution of labellings within a cyclopentane core that is reversely connected to two acyclic fragments in chlororaphen A and B.

A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation-Reprotonation Process.

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and-according to a structural model-active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations.

Isotopic labelings for mechanistic studies.

The intricate mechanisms in the biosynthesis of terpenes belong to the most challenging problems in natural product chemistry. Methods to address these problems include the structure-based site-directed mutagenesis of terpene synthases, computational approaches, and isotopic labeling experiments. The latter approach has a long tradition in biosynthesis studies and has recently experienced a revival, after genome sequencing enabled rapid access to biosynthetic genes and enzymes.

Enantioselective synthesis of all stereoisomers of geosmin and of biosynthetically related natural products.

Synthetic routes to geosmin and its enantiomer are well established, but the enantioselective synthesis of stereoisomers of geosmin is unknown. Here a stereoselective synthesis of all stereoisomers of geosmin is reported, yielding all compounds in high enantiomeric purity. Furthermore, the stereoselective synthesis of a geosmin derivative isolated from a mangrove associated streptomycete was performed, establishing the absolute configuration of the natural product.

Mechanistic characterisation of the diterpene synthase for clitopilene and identification of isopentalenene synthase from the fungus .

Two terpene synthases from the pleuromutilin producing fungus were functionally characterised. The first enzyme CpTS1 produces the new diterpene clitopilene with a novel 6-6-5-5 tetracyclic skeleton, while the second enzyme CpTS2 makes the new sesquiterpene isopentalenene. The CpTS1 reaction mechanism was studied in depth using experimental and theoretical approaches.

A General Iron-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids.

We report an iron-catalyzed decarboxylative C(sp)-O bond-forming reaction under mild, base-free conditions with visible light irradiation. The transformation uses readily available and structurally diverse carboxylic acids, iron photocatalyst, and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives as oxygenation reagents. The process exhibits a broad scope in acids possessing a wide range of stereoelectronic properties and functional groups.

Two Sesterterpene Synthases from Lentzea atacamensis Demonstrate the Role of Conformational Variability in Terpene Biosynthesis.

Mining of two multiproduct sesterterpene synthases from Lentzea atacamensis resulted in the identification of the synthases for lentzeadiene (LaLDS) and atacamatriene (LaATS). The main product of LaLDS (lentzeadiene) is a new compound, while one of the side products (lentzeatetraene) is the enantiomer of brassitetraene B and the other side product (sestermobaraene F) is known from a surprisingly distantly related sesterterpene synthase. LaATS produces six new compounds, one of which is the enantiomer of the known sesterterpene Bm1.

Mechanistic characterisation of a sesquiterpene synthase for asterisca-1,6-diene from the liverwort and implications for pentalenene biosynthesis.

A sesquiterpene synthase from the liverwort was characterised and shown to produce the new sesquiterpene hydrocarbon (3,9)-asterisca-1,6-diene, besides small amounts of pentalenene. The biosynthesis of asterisca-1,6-diene was studied through isotopic labelling experiments, giving additional insights into the long discussed biosynthesis of pentalenene.

Suberin, the hallmark constituent of bark, identified in a 45-million-year-old monkeyhair tree (Coumoxylon hartigii) from Geiseltal, Germany.

Suberin, a complex biopolymer, forms a water- and gas-insoluble barrier that protects the inner tissues of plants. It is abundant in tree bark, particularly in the cork oak Quercus suber. Anatomically, fossil bark has been described since the Devonian.

Plasmon mediated coherent population oscillations in molecular aggregates.

The strong coherent coupling of quantum emitters to vacuum fluctuations of the light field offers opportunities for manipulating the optical and transport properties of nanomaterials, with potential applications ranging from ultrasensitive all-optical switching to creating polariton condensates. Often, ubiquitous decoherence processes at ambient conditions limit these couplings to such short time scales that the quantum dynamics of the interacting system remains elusive. Prominent examples are strongly coupled exciton-plasmon systems, which, so far, have mostly been investigated by linear optical spectroscopy.

Enzymatic Synthesis of Diterpenoids from iso-GGPP III: A Geranylgeranyl Diphosphate Analog with a Shifted Double Bond.

The analog of the diterpene precursor geranylgeranyl diphosphate with a double bond shifted from C14=C15 to C15=C16 (named iso-GGPP III) has been synthesized and enzymatically converted with six bacterial diterpene synthases; this allowed the isolation of nine unnatural diterpenes. For some of the enzyme-substrate combinations, the different reactivity implemented in the substrate analog iso-GGPP III opened reaction pathways that are not observed with natural GGPP, resulting in the formation of diterpenes with novel skeletons. A stereoselective deuteration strategy was used to assign the absolute configurations of the isolated diterpenes.

Quaternary Carbon Synthesis by Titanocene Catalyzed Radical Allyl Transfer on Epoxides.

A versatile titanocene-catalyzed radical allyl transfer reaction on epoxides is reported. Epoxide opening occurs regioselectively at the more hindered side, and variously substituted allyl sulfone may be coupled to this position in an efficient manner, enabling a rapid access to quaternary carbon centers with useful functionalities for further elaboration. Furthermore, the procedure can be expanded to stereoselective variants.

Subrutilane-A Hexacyclic Sesterterpene from Streptomyces subrutilus.

Mining of a terpene synthase from Streptomyces subrutilus resulted in the identification of the hexacyclic sesterterpene subrutilane, besides eight pentacyclic side products. Subrutilane represents the first case of a saturated sesterterpene hydrocarbon. Its structure, including the absolute configuration, was unambiguously determined through X-ray crystallographic analysis and stereoselective deuteration.

A Case of Convergent Evolution: The Bacterial Sesquiterpene Synthase for 1-epi-Cubenol from Nonomuraea coxensis.

A terpene synthase from Nonomuraea coxensis was identified as (+)-1-epi-cubenol synthase. The enzyme is phylogenetically unrelated to the known enzyme of the same function that is widespread in streptomycetes. Isotopic labelling experiments were performed to unambiguously assign the NMR data and to investigate hydrogen migrations during terpene cyclisations.

Mechanistic Characterisation of Collinodiene Synthase, a Diterpene Synthase from Streptomyces collinus.

Two homologs of the diterpene synthase CotB2 from Streptomyces collinus (ScCotB2) and Streptomyces iakyrus (SiCotB2) were investigated for their products by in vitro incubations of the recombinant enzymes with geranylgeranyl pyrophosphate, followed by compound isolation and structure elucidation by NMR. ScCotB2 produced the new compound collinodiene, besides the canonical CotB2 product cyclooctat-9-en-7-ol, dolabella-3,7,18-triene and dolabella-3,7,12-triene, while SiCotB2 gave mainly cyclooctat-9-en-7-ol and only traces of dolabella-3,7,18-triene. The cyclisation mechanism towards the ScCotB2 products and their absolute configurations were investigated through isotopic labelling experiments.

Molecular Taphonomy of Heme: Chemical Degradation of Hemin under Presumed Fossilization Conditions.

The metalloporphyrin heme acts as the oxygen-complexing prosthetic group of hemoglobin in blood. Heme has been noted to survive for many millions of years in fossils. Here, we investigate its stability and degradation under various conditions expected to occur during fossilization.

Observing the Entry Events of a Titanium-Based Photoredox Catalytic Cycle in Real Time.

Titanium-based catalysis in single electron transfer (SET) steps has evolved into a versatile approach for the synthesis of fine chemicals and first attempts have recently been made to enhance its sustainability by merging it with photo-redox (PR) catalysis. Here, we explore the photochemical principles of all-Ti-based SET-PR-catalysis, i.e.

Cladosporin, A Highly Potent Antimalaria Drug?

Cladosporin, a unique natural product from the fungus Cladosporium cladosporioides, exhibits nanomolar inhibitory activity against Plasmodium falciparum by targeting its cytosolic lysyl-tRNA synthetase (PfKRS) to inhibit protein biosynthesis. Due to its exquisite selectivity towards pathogenic parasites, cladosporin has become a very promising lead compound for developing antiparasitic drugs to treat drug-resistant malaria and cryptosporidiosis infections. Here we review the recent research progress of cladosporin covering aspects of the chemical synthesis, biosynthesis, bioactivity, cellular target and structure-activity relationship.

Biosynthesis of the Sesquiterpene Kitaviridene through Skeletal Rearrangement with Formation of a Methyl Group Equivalent.

A sesquiterpene synthase from was discovered and shown to produce kitaviridene, a sesquiterpene hydrocarbon with an additional methyl group equivalent in comparison to a regular sesquiterpene. Isotopic labeling experiments together with DFT calculations gave detailed insights into the cyclization cascade toward kitaviridene and explained the formation of the additional methyl group equivalent.

Functional Characterisation of Highly Conserved and Structurally Prominent Residues of 2-Methylisoborneol Synthase.

2-Methylisoborneol is a widespread musty odourant that is produced by many bacteria including actinomycetes, cyanobacteria and myxobacteria. Two 2-methylisoborneol synthases (MIBS) that are phylogenetically distant to the known enzyme from Streptomyces coelicolor were found to be highly active for 2-methylisoborneol biosynthesis. Based on the enzyme structure and on an amino acid sequence alignment, the MIBS from S.