Creating new-to-nature carbon fixation: A guide

Synthetic biology aims at designing new biological functions from first principles. These new designs allow to expand the natural solution space and overcome the limitations of naturally evolved systems. One example is synthetic CO₂-fixation pathways that promise to provide more efficient ways for the capture and conversion of CO₂ than natural pathways, such as the Calvin Benson Bassham (CBB) cycle of photosynthesis. In this review, we provide a practical guideline for the design and realization of such new-to-nature CO₂-fixation pathways. We introduce the concept of “synthetic CO₂-fixation”, and give a general overview over the enzymology and topology of synthetic pathways, before we derive general principles for their design from their eight naturally evolved analogs. We provide a comprehensive summary of synthetic carbon-assimilation pathways and derive a step-by-step, practical guide from the theoretical design to their practical implementation, before ending with an outlook on new developments in the field.