Aliphatic hydroxylation and epoxidation of capsaicin by cytochrome P450 CYP505X

Microbial cytochrome P450 enzymes (CYPs) are able to mimic the metabolism of human CYPs. One challenge is to identify the respective drug metabolites and to compare substrate specificities to those of the human enzymes. In this study, a class VIII self-sufficient CYP from Aspergillus fumigatus (CYP505X) and variants of this enzyme were heterologously expressed in E. coli. The substrate scope of the variants was determined using active pharmaceutical ingredients (APIs) and (hetero)cyclic compounds. Capsaicin – the active compound in chili peppers – was oxidized most efficiently (4.36?μM/min) in a whole cell mediated biotransformation. The products were isolated, purified and their structures elucidated by 1D and 2D NMR. The two major metabolites showed modifications on the lipophilic side chain. Specifically, capsaicin was hydroxylated at position 8 to give (E)-8-hydroxy-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide and epoxidized at the double bond to give N-(4-hydroxy-3-methoxybenzyl)-5-(3-isopropyloxiran-2-yl)-pentanamide.     

Asymmetric total synthesis of the indole alkaloid cyclopiazonic acid and first structure-activity data

The indole alkaloid α-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) besides the terpenoids thapsigargin and artemisinin. We report here the first asymmetric total synthesis of cyclopiazonic acid by a modification of the Knight synthesis, currently the most efficient route to CPA. First structure-activity data of CPA derivatives and stereoisomers are presented and will be discussed in connection with the published crystal structures of CPA-SERCA complexes.     

Analytical prediction for multiple roll systems with negative gaps

Multiple roll coaters with deformable rolls are widely spread for the coating of thin liquid films with a wet film thickness of only a few microns and below on continuous substrates. The presented analytical solution for multiple roll systems offers for the first time the possibility to predict the performance of multiple roll coaters with a nip feed system and negative gaps. The solution is based on a previously presented solution of the authors for roll pairs and extended to multiple roll systems. The results are validated with experimental data from literature and the main influencing factors of multiple roll systems are investigated. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Influence of drying and wetting on the wave propagation in partially saturated soils

The propagation of sound waves in Del Monte sand filled by an air-water mixture is studied by a linear model. Even if it does not include an operator to describe the hysteresis of the capillary pressure curve, hysteresis is accounted for: the wave analysis is performed for the two limit cases of main drying and main wetting. In the van Genuchten law both drying and wetting data are applied. Four waves appear: one transversal wave and three longitudinal waves. For the waves driven mainly by the skeleton it could be expected that the influence of consideration of the hysteresis in the capillary pressure curve is negligible. In contrast, the numerical results for the waves driven by the pore fluids exhibit a smaller influence than expected. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

On rectangular cartograms

A rectangular cartogram is a type of map where every region is a rectangle. The size of the rectangles is chosen such that their areas represent a geographic variable (e.g., population). Good rectangular cartograms are hard to generate: The area specifications for each rectangle may make it impossible to realize correct adjacencies between the regions and so hamper the intuitive understanding of the map.

We present the first algorithms for rectangular cartogram construction. Our algorithms depend on a precise formalization of region adjacencies and build upon existing VLSI layout algorithms. Furthermore, we characterize a non-trivial class of rectangular subdivisions for which exact cartograms can be computed efficiently. An implementation of our algorithms and various tests show that in practice, visually pleasing rectangular cartograms with small cartographic error can be generated effectively.     

Synthesis of 2,3-benzoxepins by sequential cyclopropanation/ring-enlargement reactions of benzopyrylium triflates with diazoesters

Functionalized 2,3-benzoxepins were prepared by cyclopropanation of benzopyrylium triflates with diazoesters and subsequent TFA-mediated ring enlargement.     

Engineering Rieske Non‐Heme Iron Oxygenases for the Asymmetric Dihydroxylation of Alkenes

The asymmetric dihydroxylation of olefins is of special interest due to the facile transformation of the chiral diol products into valuable derivatives. Rieske non‐heme iron oxygenases (ROs) represent promising biocatalysts for this reaction as they can be engineered to efficiently catalyze the selective mono‐ and dihydroxylation of various olefins. The introduction of a single point mutation improved selectivities (≥95 %) and conversions (>99 %) towards selected alkenes. By modifying the size of one active site amino acid side chain, we were able to modulate the regio‐ and stereoselectivity of these enzymes. For distinct substrates, mutants displayed altered regioselectivities or even favored opposite enantiomers compared to the wild‐type ROs, offering a sustainable approach for the oxyfunctionalization of a wide variety of structurally different olefins.     

Identifying Mixtures of Mixtures Using Bayesian Estimation

The use of a finite mixture of normal distributions in model-based clustering allows us to capture non-Gaussian data clusters. However, identifying the clusters from the normal components is challenging and in general either achieved by imposing constraints on the model or by using post-processing procedures. Within the Bayesian framework, we propose a different approach based on sparse finite mixtures to achieve identifiability. We specify a hierarchical prior, where the hyperparameters are carefully selected such that they are reflective of the cluster structure aimed at. In addition, this prior allows us to estimate the model using standard MCMC sampling methods. In combination with a post-processing approach which resolves the label switching issue and results in an identified model, our approach allows us to simultaneously (1) determine the number of clusters, (2) flexibly approximate the cluster distributions in a semiparametric way using finite mixtures of normals and (3) identify cluster-specific parameters and classify observations. The proposed approach is illustrated in two simulation studies and on benchmark datasets. Supplementary materials for this article are available online.