Genetic instability and environmental heterogeneity present persistent challenges to the stable microbial production of reduced, value-added chemicals. In this work, the authors show that limiting oxygen availability redirects electrons from respiration toward targeted reductive pathways in Cupriavidus necator, steering growth-decoupled biotransformations. The principle is demonstrated by the conversion of acetoin to 2,3-butanediol and of glycerol to 1,3-propanediol.
In cell suspension assays under a hydrogen-containing atmosphere, anoxic conditions stabilised near-stoichiometric acetoin to 2,3-butanediol conversion at 93 percent molar efficiency despite minimal fructose consumption, indicating that the reductive pathway served as the primary sink for reducing equivalents. Under oxic conditions, rapid product re-oxidation lowered the final 2,3-butanediol titre to 2.6 mM. The same principle extended to 1,3-propanediol formation in a glycerol-kinase-deficient strain, where anoxic incubation yielded 6.6 mM 1,3-propanediol, whereas aerobic conditions suppressed accumulation despite rapid substrate uptake.
Viability assays showed that Cupriavidus necator retained above 84 percent viable cells under electron-acceptor exclusion for 144 hours, declining to about 68 percent at 312 hours and below 30 percent by 696 hours, with cell aggregation from 48 hours onward. This defined operational window, together with the lithoautotrophic capability of the organism, distinguishes the approach. By providing a metabolic configuration in which loss of production would be expected to be selectively disfavoured, oxygen-controlled redox steering offers a route toward more robust reductive biotransformations. Oxygen availability thus acts as a single, tunable lever determining whether reducing equivalents flow into reduced products or into respiration.
The study was carried out at the Institute of Technical Microbiology at Hamburg University of Technology within the Collaborative Research Centre CRC 1615 (SMART Reactors).
Vivien Jesenofsky, Janek R. Weiler, Johannes Gescher, Miriam Edel (2026). Oxygen-dependent redox control enables growth-decoupled biotransformations in Cupriavidus necator. Bioresour. Technol. 461, 135473.
