TY - JOUR TI - Golgi compartments enable controlled biomolecular assembly using promiscuous enzymes AU - Jaiman, Anjali AU - Thattai, Mukund A2 - Bassereau, Patricia A2 - Barkai, Naama A2 - Luini, Alberto VL - 9 PY - 2020 DA - 2020/06/29 SP - e49573 C1 - eLife 2020;9:e49573 DO - 10.7554/eLife.49573 UR - https://doi.org/10.7554/eLife.49573 AB - The synthesis of eukaryotic glycans – branched sugar oligomers attached to cell-surface proteins and lipids – is organized like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products. However, this variability is tightly controlled: a given eukaryotic protein type is typically associated with a narrow, specific glycan oligomer profile. Here, we use ideas from the mathematical theory of self-assembly to enumerate the enzymatic causes of oligomer variability and show how to eliminate each cause. We rigorously demonstrate that cells can specifically synthesize a larger repertoire of glycan oligomers by partitioning promiscuous enzymes across multiple Golgi compartments. This places limits on biomolecular assembly: glycan microheterogeneity becomes unavoidable when the number of compartments is limited, or enzymes are excessively promiscuous. KW - glycan synthesis KW - enzyme promiscuity KW - stochastic chemical reactions KW - self-assembly JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -