Hydrogen-Driven Cofactor Regeneration for Stereoselective Whole-Cell C=C Bond Reduction in Cupriavidus necator

Graphical Abstract

Fueled by hydrogen! Through the use of Cupriavidus necator, molecular hydrogen can be exploited for cofactor regeneration intended to drive stereoselective C=C bond reduction. Key advantages and bottlenecks that arise from using this system are identified, both of which are crucial towards establishing it as a hydrogen-driven powerhouse for greener chemistry processes.

Abstract

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. A recombinant ene-reductase was expressed 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 % enantiomeric excess. The use of hydrogen as a substrate for growth and cofactor regeneration is particularly attractive because it represents a strategy for improving atom efficiency and reducing side product formation associated with the recycling of organic cofactors.