Journal
CELL
Volume 166, Issue 1, Pages 115-125Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.05.064
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Funding
- European Research Council [SYMPAC 260392, NOVCARBFIX 646827]
- Helmsley Charitable Foundation
- Larson Charitable Foundation
- Estate of David Arthur Barton
- Anthony Stalbow Charitable Trust
- Stella Gelerman, Canada
- United States-Israel Education Foundation
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Can a heterotrophic organism be evolved to synthesize biomass from CO2 directly? So far, non-native carbon fixation in which biomass precursors are synthesized solely from CO2 has remained an elusive grand challenge. Here, we demonstrate how a combination of rational metabolic rewiring, recombinant expression, and laboratory evolution has led to the biosynthesis of sugars and other major biomass constituents by a fully functional Calvin-Benson-Bassham (CBB) cycle in E. coli. In the evolved bacteria, carbon fixation is performed via a non-native CBB cycle, while reducing power and energy are obtained by oxidizing a supplied organic compound (e.g., pyruvate). Genome sequencing reveals that mutations in flux branchpoints, connecting the non-native CBB cycle to biosynthetic pathways, are essential for this phenotype. The successful evolution of a non-native carbon fixation pathway, though not yet resulting in net carbon gain, strikingly demonstrates the capacity for rapid trophic-mode evolution of metabolism applicable to biotechnology.
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