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Adaptations and constraints associated with autotrophy in microbial metabolism

Time: Fri 2021-05-07 13.00

Location:, Solna (English)

Subject area: Biotechnology

Doctoral student: Johannes Asplund Samuelsson , Science for Life Laboratory, SciLifeLab, Systembiologi, Hudson Lab

Opponent: Professor Costas D. Maranas, The Pennsylvania State University, United States

Supervisor: Associate Professor Elton P. Hudson, Science for Life Laboratory, SciLifeLab, Skolan för kemi, bioteknologi och hälsa (CBH); Professor Adil Mardinoglu, Science for Life Laboratory, SciLifeLab, Skolan för kemi, bioteknologi och hälsa (CBH)

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Carbon dioxide (CO2) emissions from human activities are driving climate change, but the pending crisis could be mitigated by a circular carbon economy where released CO2 is recycled into commodity chemicals. Autotrophic microbes can make a contribution by producing chemicals, such as biofuels, from CO2 and renewable energy. The primary natural CO2 fixation pathway is the Calvin cycle, in which the enzyme Rubisco carboxylates ribulose-1,5-bisphosphate. The present investigation used computational systems biology methods to map adaptations and constraints in autotrophic microbial metabolism based on the Calvin cycle. First, the metabolic network of the Calvin cycle-capable photoautotrophic cyanobacterium Synechocystis was contrasted with that of heterotrophic E. coli. Intracellular metabolite concentration ranges differed, leading to different capacity to provide thermodynamic driving forces to chemical production pathways. Second, the Calvin cycle in Synechocystis was modeled kinetically, showing that certain enzyme saturation and metabolite levels, for example high ribulose-1,5-bisphosphate concentration, were detrimental to stability. Control over reaction rates was distributed, but making certain enzymes faster, for example fructose-1,6-bisphosphatase, could increase overall carbon fixation rate. Third, Synechocystis was starved of CO2 and ribosome profiling was used to track the effect on translation. Stress response and CO2 uptake were upregulated, but constant Rubisco expression and ribosome pausing in 5' untranslated regions indicated readiness for reappearance of CO2. Finally, microbial genomes with and without the Calvin cycle were contrasted, revealing metabolic, energetic, and regulatory adaptations that describe the properties of a functional autotroph. These findings provide a background for future study and engineering of autotrophs for direct conversion of CO2 into commodity chemicals.