Redox poise in R. rubrum phototrophic growth drives large-scale changes in macromolecular pathways

Area of Science:

• Microbiology
• Biochemistry
• Systems Biology

Background:

• Purple nonsulfur bacteria, like Rhodospirillum rubrum, utilize photoheterotrophic growth on organic substrates.
• Electron acquisition occurs via organic/inorganic substrate oxidation or reverse electron flow.
• Cellular redox poise (oxidized to reduced cofactor ratio) and reducing equivalent dissipation are complex and poorly understood.

Purpose of the Study:

• To model and understand the redox poise during photoheterotrophic growth.
• To investigate the impact of redox conditions on cellular biosynthesis and macromolecule levels.
• To clarify the roles of reverse electron flow and ATP in cofactor reduction.

Main Methods:

• Physics-based modeling capturing mass action kinetics and thermodynamics.
• Evaluation of a range of redox conditions, from thermodynamic equilibrium to far-from-equilibrium.
• Integration of modeling predictions with experimental measurements.

Main Results:

• Redox poise significantly alters biosynthetic pathway activity and macromolecule composition (DNA, RNA, proteins, fatty acids).
• Reverse electron flow is a minor contributor to reduced cofactor production compared to substrate oxidation.
• The quinone pool primarily supports ATP production, which drives reductions via ATP hydrolysis, even with low NADP+/NADPH.

Conclusions:

• Cellular redox poise is a critical regulator of biosynthesis and macromolecule levels in photoheterotrophic bacteria.
• ATP hydrolysis, coupled with reductive processes, plays a key role in managing cellular redox balance.
• The dynamic interplay between nucleotide, lipid, and protein production is a significant mechanism for balancing cellular oxidation and reduction.