Hydrogen-driven cofactor regeneration for stereoselective whole-cell C=C bond reduction in Cupriavidus necator

The coupling of recombinantly expressed oxidoreductases to endogenous hydrogenases for cofactor‐recycling permits the omission of organic cosubstrates as sacrificial electron donors in whole‐cell biotransformations. This increases atom efficiency and simplifies the reaction. We have expressed a recombinant ene‐reductase in the hydrogen‐oxidizing proteobacterium Cupriavidus necator H16. In hydrogen‐driven biotransformations, whole cells catalyzed asymmetric C=C bond reduction of unsaturated cyclic ketones with stereoselectivities up to >99% ee. The use of hydrogen as a substrate for growth and cofactor regeneration is particularly attractive as it represents a strategy for improving atom efficiency and reducing side product formation associated with the recycling of organic cofactors.