Constructing and prototyping new biology in vitro
Nature is a great tinkerer. However, during the course of evolution, it has explored the theoretically possible solution space only sparsely, which has left many possibilities untested. Using the methods of synthetic biology makes it possible to realize these solutions today. In our group, we have focused on designing and realizing de novo CO2 fixation pathways that are of improved efficiency compared to those evolved by nature. These efforts involve:
- a theoretical phase, in which we design these new-to-nature pathways through a process called metabolic retrosynthesis, followed by thermodynamic and flux analysis to evaluate those solutions
- a reconstruction phase that involves the identification and/or design of all enzymes required to build the solutions in vitro
- an optimization phase, in which we operate and optimize the pathways in iterative design-build-test-rounds
Through these efforts, we have already demonstrated several new-to-nature solutions that are able to improve photosynthesis (i.e., trough new-to-nature photorespiration pathways, such as the TaCo pathway; Scheffen et al. Nat Catal), or even replace photosynthesis through more efficient solutions, such as the CETCH, HOPAC or Theta cycles (Schwander et al. Science; McLean et al. Sci Adv).
We also established new workflows such as METIS that combine machine learning with lab automation and have allowed us to dramatically increase in vitro pathway optimization (Pandi et al. Nat Comm), recently also through the help of in vitro transcription/translation (TXTL) methods (Pandi et al. Nat Comm). Our optimized synthetic pathways are then either extended to allow for the synthesis of more complex compounds from CO2 (i.e., value added products, such as terpenes or polyketides; Diehl el al. Nat Chem Biol). In parallel, we aim at realizing the most promising solutions inside a cellular context, which can be a natural cell (Luo et al. Nat Catal), or artificial organelles and cells that we develop (Miller et al. Science).
Learn more about:
Evolution and Biochemistry of natural CO2-fixing enzymes
Engineering of new-to-nature CO2- and C1-converting enzymes
Transplantation of new CO2-metabolism into natural cells
Phototrophic chassis
Design and realization of artificial organelles and cells
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