Bioenergetic trade-offs can reveal the path to superior microbial CO2 fixation pathways

Biotechnology can lead to cost-effective processes for capturing CO ₂ using the natural or genetically engineered metabolic capabilities of microorganisms. However, introducing desirable genetic modifications into microbial strains without compromising their fitness (growth yield and rate) during industrial-scale cultivation remains a challenge. Recently, a computational methodology was developed that considers the trade-offs between energy efficiency (yield) and growth rate, allowing us to evaluate candidate metabolic modifications in silico for microbial conversions. A comprehensive optimisation of known prokaryotic autotrophic CO ₂ fixation pathways was conducted, considering all possible variants under different environmental conditions. The results revealed the superior configurations in terms of both yield (efficiency) and rate (driving force). This approach and results can guide optimal pathway configurations for enhanced prokaryotic carbon fixation through metabolic engineering. By aligning strain modifications with these theoretically revealed near-optimal pathway configurations, we can optimally engineer strains of good fitness under open culture industrial scale conditions.