It's estimated that more than 90% of CO2 is captured (or ‘fixed’) through the Calvin cycle of photosynthesis and its key enzyme, RuBisCO. It’s the most prevalent carbon-fixing metabolic pathway across plants and microbes, but only one of many that exist in nature. Dr. Erb and colleagues have so far discovered several previously undescribed carbon-fixing microbial pathways and enzymes, including a new class of enoyl-CoA carboxylases/reductases (ECRs) [9, 10]. They are the most efficient CO2 converting enzymes found to date, and up to twenty times more productive than RuBisCO.
Analysis of these ECRs to fully understand their structure and mechanisms in fine detail has given rise to the creation of a new raft of potent and versatile, bioengineered counterparts. But naturally occurring carbon-fixing metabolic pathways are complex, with numerous moving parts. The process of capturing CO2 and converting it into useful carbohydrates is not the work of one single enzyme, but a carefully choreographed dance of many.
Metabolic retrosynthesis is the next step beyond optimizing individual enzymes. It’s the science of engineering entirely new synthetic pathways of CO2 conversion, building them from scratch using known enzymes from across the natural world, and filling in the gaps with novel proteins.
The discovery of ECRs allowed Dr. Erb’s lab, for instance, to successfully create the ‘CETCH cycle’ — a pathway comprising 17 enzymes, 14 of which were sourced from nine different organisms, with three engineered proteins completing the design [11]. The rates of carbon fixation of the CETCH cycle are 20 times higher than that of natural photosynthesis, and it uses 20% less energy per CO2 fixed.
The ‘TaCo pathway’ is another synthetic system, which includes three bioengineered enzymes, including a completely novel carbon-fixing enzyme. It has been developed to fix the inefficiencies of photorespiration, an undesirable step in natural photosynthesis that sees roughly 25% of fixed carbon re-released as CO2. Rather than simply plugging this leak, the TaCo pathway reduces the energy demands of photorespiration and increases carbon efficiency by up to 150%, turning it into a carbon-capturing process [12, 13].