Enzymes dependent on nicotinamide cofactors are important components of the expanding range of asymmetric synthetic techniques. New challenges in asymmetric catalysis are arising in the field of deuterium labelling, where compounds bearing deuterium ( 2 H) atoms at chiral centres are becoming increasingly desirable targets for pharmaceutical and analytical chemists. However, utilisation of NADH-dependent enzymes for 2 H-labelling is not straightforward, owing to difficulties in supplying a suitably isotopically-labelled cofactor ([4-2 H]-NADH). Here we report on a strategy that combines a clean reductant (H 2 ) with a cheap source of 2 H-atoms ( 2 H 2 O) to generate and recycle [4-2 H]-NADH. By coupling [4-2 H]-NADH-recycling to an array of C=O, C=N, and C=C bond reductases, we demonstrate asymmetric deuteration across a range of organic molecules under ambient conditions with near-perfect chemo-, stereo-and isotopic selectivity. We demonstrate the synthetic utility of the system by applying it in the isolation of the heavy drug (1S,3'R)-[2',2',3'-2 H 3 ]solifenacin fumarate on a preparative scale.

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has made ap rovisionalp atent application based on the discoveries demonstrated in this manuscript.Keywords: antiviral agents · nucleotide analogues · radical-SAM enzyme · tyrosyl radicals · viperin Figure 6. The proposed mechanism of catalysis by TtRSAD2. The 5'-dAdo radicalabstractst he Ha tom (red) at the C4' position of ribose to generate a C4'-centred radical intermediate. As ar esult of hyperconjugation between a po rbitalonC 4' and the s C3'ÀO3' orbital, assisted by ap rotein amino acid residue( AH), the 3'-OHg roupo ft he riboseforms awater molecule. The proton to generate the water molecule is provided by tyrosine either indirectly through ap roton hoppingp athway(1) or directly (2). Spontaneously, an electron from tyrosine reduces the substrate-radical intermediate. As a result, the nucleotide analogue product and ap rotein tyrosylradical are formed. The [4 FeÀ4S] 2 + clusteri sre-reduced and then,t he tyrosyl radicali s reducedbya ne lectron from the [4 FeÀ4S] + cluster.

Edited by Peter BrzezinskiViperin (RSAD2) is an antiviral radical S-adenosylmethionine (SAM) enzyme highly expressed in different cell types upon viral infection. Recently, it has been reported that the radical-SAM activity of viperin transforms cytidine triphosphate (CTP) to its analogue 3 0 -deoxy-3 0 ,4 0 -didehydro-CTP (ddhCTP). Based on biochemical studies and cell biological experiments, it was concluded that ddhCTP and its nucleoside form ddhC do not affect the cellular concentration of nucleotide triphosphates and that ddhCTP acts as replication chain terminator. However, our re-evaluation of the reported data and new results indicate that ddhCTP is not an effective viral chain terminator but depletes cellular nucleotide pools and interferes with mitochondrial activity to inhibit viral replication. Our analysis is consistent with a unifying view of the antiviral and radical-SAM activities of viperin.

We manipulate and verify the redox state of single metalloprotein crystals by combining electrochemical control with synchrotron infrared microspectroscopy.

The high selectivity of biocatalysis offers a valuable method for greener, more efficient production of enantiopure molecules. Operating immobilised enzymes in flow reactors can improve the productivity and handling of biocatalysts, and using H2 gas to drive redox enzymes bridges the gap to more traditional metal‐catalysed hydrogenation chemistry. Herein, we describe examples of H2‐driven heterogeneous biocatalysis in flow employing enzymes immobilised on a carbon nanotube column, achieving near‐quantitative conversion in <5 min residence time. Cofactor recycling is carried out in‐situ using H2 gas as a clean reductant, in a completely atom‐efficient process. The flow system is demonstrated for cofactor conversion, reductive amination and ketone reduction, and then extended to biocatalytic deuteration for the selective production of isotopically labelled chemicals.

Thermochemical processing methods such as pyrolysis are of growing interest as a means of converting biomass into fuels and commodity chemicals in a sustainable manner. Macroalgae, or seaweed, represent a novel class of feedstock for pyrolysis that, owing to the nature of the environments in which they grow coupled with their biochemistry, naturally possess high metal contents. Although the impact of metals upon the pyrolysis of terrestrial biomass is well documented, their influence on the thermochemical conversion of marine-derived feeds is largely unknown. Furthermore, these effects are inherently difficult to study, owing to the heterogeneous character of natural seaweed samples. The work described in this paper uses copper(II) alginate, together with alginic acid and sodium alginate as model compounds for exploring the effects of metals upon macroalgae thermolysis. A thermogravimetric analysis–Fourier transform infrared spectroscopic study revealed that, unusually, Cu 2+ ions promote the onset of pyrolysis in the alginate polymer, with copper(II) alginate initiating rapid devolatilization at 143°C, 14°C lower than alginic acid and 61°C below the equivalent point for sodium alginate. Moreover, this effect was mirrored in a sample of wild Laminaria digitata that had been doped with Cu 2+ ions prior to pyrolysis, thus validating the use of alginates as model compounds with which to study the thermolysis of macroalgae. These observations indicate the varying impact of different metal species on thermochemical behaviour of seaweeds and offer an insight into the pyrolysis of brown macroalgae used in phytoremediation of metal-containing waste streams.