Engineering new-to-nature biochemical conversions by combining fermentative metabolism with respiratory modules

Anaerobic microbial fermentations are a cornerstone of industrial bio-based processes, but redox balancing limits substrate-product combinations. This research designs an aerobic fermentative metabolism incorporating respiratory modules to re-balance unbalanced fermentations. An engineered *E. coli* strain aerobically ferments glucose to lactate, and glycerol fermentation to lactate is demonstrated by reintegrating glycerol 3-phosphate dehydrogenase. The design's potential is shown by redirecting fermentative flux from glycerol to isobutanol production. This approach overcomes limitations imposed by traditional redox balancing in highly efficient microbial fermentation.

Helena Schulz-Mirbach, Jan Lukas Krüsemann, Theofania Andreadaki, Jana Natalie Nerlich, Eleni Mavrothalassiti, Simon Boecker, Philipp Schneider, Moritz Weresow, Omar Abdelwahab, Nicole Paczia, Beau Dronsella, Tobias J. Erb, Arren Bar-Even, Steffen Klamt, Steffen N. Lindner