RT Journal Article SR Electronic T1 Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.03.06.531353 DO 10.1101/2023.03.06.531353 A1 Ying Gu A1 Sara Alam A1 Snezhana Oliferenko YR 2023 UL http://biorxiv.org/content/early/2023/03/07/2023.03.06.531353.abstract AB Cellular metabolism relies on just a few redox cofactors. Selective compartmentalization may prevent competition between metabolic reactions requiring the same cofactor. Is such compartmentalization necessary for optimal cell function? Is there an optimal compartment size? Here we probe these fundamental questions using peroxisomal compartmentalization of the last steps of lysine and histidine biosynthesis in the fission yeast Schizosaccharomyces japonicus. We show that compartmentalization of these NAD+ dependent reactions together with a dedicated NADH/NAD+ recycling enzyme supports optimal growth when an increased demand for anabolic reactions taxes cellular redox balance. In turn, compartmentalization constrains the size of individual organelles, with larger peroxisomes accumulating all the required enzymes but unable to support both biosynthetic reactions at the same time. We propose that compartmentalized biosynthetic reactions are sensitive to the size of the compartment, likely due to scaling-dependent changes within the system, such as enzyme packing density.Competing Interest StatementThe authors have declared no competing interest.