Genomic Science Program
U.S. Department of Energy | Office of Science | Biological and Environmental Research Program

Prototyping Carbon-Conserving Networks for Diacid Production

Authors:

Ray Westenberg1,2*, Garrett Helwig2, James Carothers4,5, Pamela Peralta-Yahya1,2,3

Institutions:

1Bioengineering Program, Georgia Institute of Technology; 2School of Chemical and Biomolecular Engineering, Georgia Institute of Technology; 3School of Chemistry and Biochemistry, Georgia Institute of Technology; 4Molecular Engineering and Sciences Institute and Center for Synthetic Biology, University of Washington; 5Department of Chemical Engineering, University of Washington

Abstract

Decarboxylation, the loss of carbon dioxide (CO2) from a compound, is used in metabolism to commit carbon flux to a specific pathway. However, decarboxylation also limits the product carbon yield, with acetyl-CoA (two C2) achieving only 66% carbon recovery when routing glucose (C6) via glycolysis and oxidative decarboxylation. Carbon-conservation networks (CCNs) that circumvent CO2 release can theoretically lead to carbon and product yields beyond those seen with endogenous metabolism (Westenberg and Peralta-Yahya 2023). Engineering metabolic pathways and developing technologies to improve carbon yield has the potential to increase the economic viability of large-volume low-cost chemicals. Toward this goal, the effects of overlaying CCNs have been mathematically modeled onto the endogenous metabolism of non-model organisms, such as Pseudomonas putida and Rhodobacter sphaeroides. The model predictions and prototyping combinations of existing and de novo CCNs predicted to improve carbon and product yields are now being implemented. As a proof-of-concept, the research team is measuring the effects of CCNs on the production of industrially relevant diacids: malic and itaconic. Going forward, the generality of CCNs will enable their implementation toward production of other large-scale chemicals that suffer from metabolic carbon loss.

References

Westenberg, R., and P. Peralta-Yahya. 2023. “Toward Implementation of Carbon-Conservation Networks in Nonmodel Organisms,” Current Opinion in Biotechnology 81, 102949. DOI:10.1016/j.copbio.2023.102949.