The climate emergency has intensified the need for innovative solutions for CO2 capture and conversion. Synthetic biology offers new avenues for designing CO2-fixation pathways that are more efficient than those found in nature. However, implementing these new pathways in various in vitro and in vivo systems poses significant challenges. The group led by Tobias Erb has made a breakthrough in this field by designing and constructing a new synthetic CO2-fixation pathway, named the THETA cycle.
The THETA cycle is distinctive in its ability to convert two CO2 molecules into one molecule of acetyl-CoA in a single cycle. Acetyl-CoA is a central metabolite in nearly all forms of cellular metabolism and is crucial for the synthesis of various biomolecules, including biofuels, biomaterials, and pharmaceuticals. This makes it an exceptionally valuable compound in biotechnological applications.
The cycle was designed around two of the fastest known CO2-fixing enzymes: crotonyl-CoA carboxylase/reductase and phosphoenolpyruvate carboxylase. These powerful biocatalysts, found in bacteria, can capture CO2 more than ten times faster than the enzyme RubisCO, which is responsible for CO2 fixation in chloroplasts during natural photosynthesis.
In the laboratory, the functionality of the THETA cycle was confirmed in test tubes. Following this, the researchers embarked on a series of rational and machine learning-guided optimizations, which led to a hundredfold increase in the acetyl-CoA yield. The next critical step was to test its feasibility in vivo, for which the cycle was divided into three modules. Each module was successfully incorporated into E. coli, and their functionality was verified through growth-coupled selection and isotopic labelling.
Shanshan Luo, the lead author of the study, highlighted the uniqueness of the cycle, stating, "What is special about this cycle is that it contains several intermediates that serve as central metabolites in the bacterium's metabolism. This overlap offers the opportunity to develop a modular approach for its implementation." Luo noted the successful demonstration of the three individual modules in E. coli but also acknowledged that closing the entire cycle in vivo remains a significant challenge, given the need to synchronize the 17 reactions with the natural metabolism of E. coli, which involves hundreds to thousands of reactions.
Despite these challenges, Luo sees great potential in the cycle, envisioning it as a versatile platform for producing valuable compounds directly from CO2 by extending its output molecule, acetyl-CoA.
Tobias Erb emphasized the importance of this achievement in the field of synthetic biology. "Bringing parts of the THETA cycle into living cells is an important proof-of-principle," he said. "Such modular implementation of this cycle in E. coli paves the way to the realization of highly complex, orthogonal new-to-nature CO2-fixation pathways in cell factories. We are learning to completely reprogram the cellular metabolism to create a synthetic autotrophic operating system for the cell."
This research not only demonstrates a novel approach to CO2 fixation but also opens the door to potentially transformative applications in biotechnology, addressing the urgent need for sustainable solutions in the face of the global climate crisis.
Research Report:Construction and modular implementation of the THETA cycle for synthetic CO2 fixation. Nature Catalysis, 6(12), 1228-1240.
Related Links
Max Planck Institute for Terrestrial Microbiology
Carbon Worlds - where graphite, diamond, amorphous, fullerenes meet
| Subscribe Free To Our Daily Newsletters |
| Subscribe Free To Our Daily Newsletters |
