Perspective: a stirring role for metabolism in cells.

Based on recent findings indicating that metabolism might be governed by a limit on the rate at which cells can dissipate Gibbs energy, in this Perspective, we propose a new mechanism of how metabolic activity could globally regulate biomolecular processes in a cell. Specifically, we postulate that Gibbs energy released in metabolic reactions is used to perform work, allowing enzymes to self-propel or to break free from supramolecular structures. This catalysis-induced enzyme movement will result in increased intracellular motion, which in turn can compromise biomolecular functions.

goes through distinct metabolic phases during its replicative lifespan.

A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Previously, we mapped age-related changes in the proteome and transcriptome (Janssens et al., 2015).

An upper limit on Gibbs energy dissipation governs cellular metabolism.

The principles governing cellular metabolic operation are poorly understood. Because diverse organisms show similar metabolic flux patterns, we hypothesized that a fundamental thermodynamic constraint might shape cellular metabolism. Here, we develop a constraint-based model for Saccharomyces cerevisiae with a comprehensive description of biochemical thermodynamics including a Gibbs energy balance.

An engineered Calvin-Benson-Bassham cycle for carbon dioxide fixation in Methylobacterium extorquens AM1.

Organisms are either heterotrophic or autotrophic, meaning that they cover their carbon requirements by assimilating organic compounds or by fixing inorganic carbon dioxide (CO). The conversion of a heterotrophic organism into an autotrophic one by metabolic engineering is a long-standing goal in synthetic biology and biotechnology, because it ultimately allows for the production of value-added compounds from CO. The heterotrophic Alphaproteobacterium Methylobacterium extorquens AM1 is a platform organism for a future C1-based bioeconomy.