Each year, more than 350 gigatons of carbon dioxide are converted to biomass by autotrophs, sustaining life on Earth with reduced carbon compounds. The rate limiting enzyme of carbon dioxide assimilation is called RubisCO, which is remarkably slow and inefficient, wasting huge amounts of the energy harvested from the sun. COOFIX aims to design a novel enzyme that can fix carbon dioxide into the metabolic intermediate oxalate in a single step. COOFIX employ a highly interdisciplinary approach, combining biochemistry, spectroscopy, structural biology and computational chemistry in an innovative manner to accomplish the project objectives. Binuclear organometallic copper complexes are capable of reducing carbon dioxide to oxalate with high selectivity, and this functionality will be engineered in type-3 copper protein active sites. An autotrophic model organism will be engineered to accommodate our novel carbon dioxide reductase and to convert the enzyme product oxalate to biomass. A novel method of computer assisted enzyme engineering is proposed to efficiently improve our carbon dioxide reducing enzyme. Current computational engineering methods are limited by inefficient sampling of fluctuating protein structures along the evolutionary path. COOFIX combine hardware and software accelerated molecular dynamics simulations with machine learning to address this challenge. COOFIX will contribute to groundbreaking discoveries in the fields of synthetic biology and enzyme engineering. It will also impact carbon dioxide feedstock utilization, providing novel opportunities to accumulate valuable organic molecules from this surplus and underexploited resource.
Project leader: Åsmund Røhr Kjendseth
Institution: FAKULTET FOR KJEMI, BIOTEKNOLOGI OG MATVITENSKAP