Conversion of CO ₂ into organic acids by engineered autotrophic yeast

The increase of CO 2 emissions due to human activity is one of the preeminent reasons for the present climate crisis. In addition, considering the increasing demand for renewable resources, the upcycling of CO 2 as a feedstock gains an extensive importance to establish CO 2 -neutral or CO 2 -negative industrial processes independent of agricultural resources. Here we assess whether synthetic autotrophic Komagataella phaffii ( Pichia pastoris ) can be used as a platform for value-added chemicals using CO 2 as a feedstock by integrating the heterologous genes for lactic and itaconic acid synthesis. 13 C labeling experiments proved that the resulting strains are able to produce organic acids via the assimilation of CO 2 as a sole carbon source. Further engineering attempts to prevent the lactic acid consumption increased the titers to 600 mg L −1 , while balancing the expression of key genes and modifying screening conditions led to 2 g L −1 itaconic acid. Bioreactor cultivations suggest that a fine-tuning on CO 2 uptake and oxygen demand of the cells is essential to reach a higher productivity. We believe that through further metabolic and process engineering, the resulting engineered strain can become a promising host for the production of value-added bulk chemicals by microbial assimilation of CO 2 , to support sustainability of industrial bioprocesses.