<p></p><p>Chemicals labelled with the heavy hydrogen isotope
deuterium (<sup>2</sup>H) have long been used in chemical and biochemical
mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration
of selectively deuterated drug candidates that exhibit advantageous pharmacological
traits has spurred innovations in metal-catalysed <sup>2</sup>H insertion at
targeted sites, but asymmetric deuteration remains a key challenge. Here we
demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving
high chemo-, enantio- and isotopic selectivity, requiring only <sup>2</sup>H<sub>2</sub>O
(D<sub>2</sub>O) and unlabelled dihydrogen under ambient conditions. The vast
library of enzymes established for NADH-dependent C=O, C=C, and C=N bond
reductions have yet to appear in the toolbox of commonly employed <sup>2</sup>H-labelling
techniques due to requirements for suitable deuterated reducing equivalents. By
facilitating transfer of deuterium atoms from <sup>2</sup>H<sub>2</sub>O
solvent to NAD<sup>+</sup>, with H<sub>2</sub> gas as a clean reductant, we
open up biocatalysis for asymmetric reductive deuteration as part of a
synthetic pathway or in late stage functionalisation. We demonstrate
enantioselective deuteration via ketone and alkene reductions and reductive
amination, as well as exquisite chemo-control for deuteration of compounds with
multiple unsaturated sites.</p><p></p>
Energy-dependent accumulation of iron by isolated rat liver mitochondria. Requirement of reducing equivalents and evidence for a unidirectional flux of Fe(II) across the inner membrane
