Periodic Reporting for period 2 - ConCO2rde (Training network on the conversion of CO2 by smart autotrophic biorefineries)
Reporting period: 2023-01-01 to 2024-12-31
With a growing world population, depleting fossil resources and ongoing climate change, innovative new approaches are needed to reintegrate the greenhouse gas carbon dioxide into a circular economy and provide sustainable sources of energy and materials for future generations. An important step towards a carbon-neutral bioeconomy is the valorization of carbon dioxide as a feedstock. Most commodity chemicals are still derived exclusively from fossil resources such as oil, natural gas and coal. Biomanufacturing through fermentation enables the sustainable, targeted production of desired chemicals using "above-ground" carbon sources.
Recently, several routes for the direct utilization of carbon dioxide have been proposed, including autotrophic microorganisms with the natural ability to grow on C1 compounds, synthetic carbon dioxide fixation pathways, and the design of synthetic autotrophs. While the various engineered synthetic pathways for carbon dioxide utilization seem promising in terms of efficiency and modularity, these approaches mostly suffer from reduced energy supply, compartmentalization, host selection, and net carbon dioxide assimilation.
ConCO2rde's goal was to harness the power of autotrophic microorganisms to use renewable energy (e.g. green hydrogen) for the accumulation of biomass directly from carbon dioxide to synthesize valuable chemicals with much lower environmental impact. To achieve this goal, ConCO2rde has leveraged complementary expertise in synthetic biology, metabolic engineering, biocatalysis and process engineering, with strong participation from industrial partners. ConCO2rde trained 11 Early Stage Researchers (ESRs) in cutting-edge research projects on (i) the combination of synthetic biology with metabolic and process engineering to create an efficient pathway from carbon dioxide fixation to chemical production, (ii) the application of hydrogen-driven biotransformations using redox enzymes for the synthesis of high-value chemicals, and (iii) the development of novel reactor concepts for gas fermentations using hydrogen, carbon dioxide and oxygen towards commercially relevant processes. The close interaction between academia and industry was crucial in qualifying these young scientists to take up decision-making positions within the European biotech sector and make a difference for sustainability and the circular carbon bioeconomy. Overall, ConCO2rde's interdisciplinary consortium of 17 leading academic and private organizations provided the ideal environment to foster complementary expertise in synthetic biology, metabolic engineering, biocatalysis and process engineering, while providing 11 young researchers with in-depth training in an interdisciplinary working environment, strengthened by transferable skills training with strong industrial participation.
Recently, several routes for the direct utilization of carbon dioxide have been proposed, including autotrophic microorganisms with the natural ability to grow on C1 compounds, synthetic carbon dioxide fixation pathways, and the design of synthetic autotrophs. While the various engineered synthetic pathways for carbon dioxide utilization seem promising in terms of efficiency and modularity, these approaches mostly suffer from reduced energy supply, compartmentalization, host selection, and net carbon dioxide assimilation.
ConCO2rde's goal was to harness the power of autotrophic microorganisms to use renewable energy (e.g. green hydrogen) for the accumulation of biomass directly from carbon dioxide to synthesize valuable chemicals with much lower environmental impact. To achieve this goal, ConCO2rde has leveraged complementary expertise in synthetic biology, metabolic engineering, biocatalysis and process engineering, with strong participation from industrial partners. ConCO2rde trained 11 Early Stage Researchers (ESRs) in cutting-edge research projects on (i) the combination of synthetic biology with metabolic and process engineering to create an efficient pathway from carbon dioxide fixation to chemical production, (ii) the application of hydrogen-driven biotransformations using redox enzymes for the synthesis of high-value chemicals, and (iii) the development of novel reactor concepts for gas fermentations using hydrogen, carbon dioxide and oxygen towards commercially relevant processes. The close interaction between academia and industry was crucial in qualifying these young scientists to take up decision-making positions within the European biotech sector and make a difference for sustainability and the circular carbon bioeconomy. Overall, ConCO2rde's interdisciplinary consortium of 17 leading academic and private organizations provided the ideal environment to foster complementary expertise in synthetic biology, metabolic engineering, biocatalysis and process engineering, while providing 11 young researchers with in-depth training in an interdisciplinary working environment, strengthened by transferable skills training with strong industrial participation.
After the successful recruitment of 11 highly talented young scientists, the first phase of ConCO2rde was dedicated to the establishment of genetic tools, strains and reactors, as well as the first experimental proof of concepts. Despite the COVID pandemic, the ESRs showed remarkable progress in developing novel approaches for autotrophic processes to produce the desired products. In addition, several secondments to the academic partner universities and industrial partners as well as intensive discussions at project meetings with participants from the private sector and the Industrial Biotechnology Cluster allowed a clear orientation of the research towards innovation and technical implementation. The double degree structure of the project provided a framework for highly interdisciplinary research at the interface of synthetic biology, metabolic engineering, biocatalysis and process engineering. Overall, the ConCO2dre consortium succeeded in engineering autotrophic microorganisms - e.g. by overcoming genetic barriers, implementing rapid cloning systems, and optimizing metabolic pathways - ultimately enabling the efficient production of chemicals such as L-methionine, indigo, and isopropanol. Enzyme-based strategies have been refined to facilitate the synthesis of complex molecules, including N-heterocyclic compounds, by enhancing enzyme activity under lithoautotrophic conditions and integrating bioelectrochemical systems for enhanced electron transfer. Innovative process intensification methods, including novel gas fermentation systems, membrane contactor technologies, and high cell density bioreactors, have led to improved gas transfer, reactor efficiency, and safety through operation in reduced hydrogen atmospheres. In addition, dedicated efforts to understand and manage population heterogeneity have led to the development of biosensors that monitor the dynamics of production subpopulations. This work has provided valuable insights into how cultivation modes and induction protocols affect process performance, enabling more robust and consistent bioprocessing. Taken together, these achievements demonstrate the potential of a highly flexible microbial platform for the sustainable production of a wide range of chemicals - from bulk commodities to high-value fine chemicals - marking a decisive step towards efficient, CO2-based biotechnological processes and a carbon-neutral bioeconomy.
The results of ConCO2rde are expected to promote the implementation of autotrophic microorganisms in biotechnology, which may hold the key to harnessing biology's synthetic ability to directly convert atmospheric carbon dioxide into more complex molecules to produce fuels, plastics or pharmaceuticals. The results of ConCO2rde showcased innovative and applicable biotechnological solutions that enable the direct use of carbon dioxide (e.g. from industrial waste gases) as a resource to produce chemicals, pharmaceuticals, or food/feed ingredients, powered by energy derived from hydrogen. The holistic way to harness autotrophic microorganisms and implement them in industrial scale production requires not only the combination of synthetic biology, metabolic engineering, biocatalysis and process engineering, but also intensive interaction with the private sector to facilitate cross-sector discussions and exchange of ideas through secondments to the various industrial partners. ConCO2rde demonstrated the generation of novel strains that utilize hydrogen and carbon dioxide to produce valuable chemicals, as well as important optimization steps to improve autotrophic cultivations. In addition, the interdisciplinary collaboration between the partners enhanced our understanding of the physiological parameters that determine strain behavior, the evaluation of strain performance under autotrophic conditions, and their further optimization for efficient synthesis of various chemicals directly from carbon dioxide. These findings are critical to turning "invention into innovation" and paving the way for the implementation of customized autotrophic strains in large-scale biotechnological production. In addition, along with the project execution, several research papers have been published, with many other publications in preparation/revision. The interdisciplinary research and the intensive interaction with the academic and private sector are very positive aspects for such a double degree program, with the training of our 11 young scientists at the center of the activities.