Metagenomic ene-reductases for the bioreduction of sterically challenging enones

Ene-reductases (ERs) of the Old Yellow Enzyme family catalyse asymmetric reduction of activated alkenes providing chiral products. They have become an important method in the synthetic chemists' toolbox offering a sustainable alternative to metal-catalysed asymmetric reduction. Development of new biocatalytic alkene reduction routes, however needs easy access to novel biocatalysts. A sequence-based functional metagenomic approach was used to identify novel ERs from a drain metagenome. From the ten putative ER enzymes initially identified, eight exhibited activities towards widely accepted mono-cyclic substrates with several of the ERs giving high reaction yields and stereoselectivities. Two highly performing enzymes that displayed excellent co-solvent tolerance were used for the stereoselective reduction of sterically challenging bicyclic enones where the reactions proceeded in high yields, which is unprecedented to date with wild-type ERs. On a preparative enzymatic scale, reductions of Hajos–Parish, Wieland–Miescher derivatives and a tricyclic ketone proceeded with good to excellent yields

Simulation of polarity independent RESET in electrochemical metallization memory cells

Redox-based resistive switching devices are a potential candidate for future non-volatile memory. One type of these devices is the electrochemical metallization cell (ECM), which typically exhibit a bipolar operation scheme. However, at high current levels a transition to polarity independent RESET switching has been observed. This work presents a numerical simulation model of the RESET operation in ECM cells, which is capable of explaining the occurrence of polarity-independent RESET switching. The model is based on the thermally activated electrochemical dissolution of a conducting filament. © 2013 IEEE

Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis

The benzylisoquinoline alkaloids (BIAs) are an important group of higher plant secondary metabolites, which have been reported to show significant pharmaceutical activities. The production of BIAs via synthetic biology approaches provides a higher yielding strategy compared to traditional synthetic methods and plant isolation methods. However, the reconstruction of BIAs pathways in microorganisms combining heterologous enzymes can also give access to BIAs via cascade reactions. Most importantly, non‐natural BIAs can be generated through such artificial pathways. In the current study, we describe new tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non‐natural alkaloids, in cascades from L‐tyrosine and analogues