Pareto-optimal synthesis of multiple glycans in Golgi compartments

Glycans are tree-shaped sugar chains covalently bonded to proteins in the plasma membrane of eukaryotic cells. They are assembled step by step through monomer addition reactions in different compartments of the Golgi apparatus. Glycans engage in multiple functions at the cell-surface, making their correct manufacture to be of vital importance.

The enzyme distribution across Golgi compartments and the residence time of a glycan in each compartment have a marked effect on the amount of correct glycans manufactured, or the glycan yield. We model the synthesis of glycans in the eukaryotic Golgi apparatus, with a focus on optimizing this glycan yield. In particular, we explore strategies for the simultaneous synthesis of multiple glycans. Each strategy corresponds to a particular choice of how enzymes are split across Golgi compartments with defined residence times. We explicitly include the effect of undesirable reactions, which inevitably occur due to enzyme promiscuity. We find there is often a tradeoff in the achievable yield of distinct glycans. We explore this tradeoff using a Pareto optimality framework, and demonstrate that Pareto optimality can be a valuable aid in studying glycan manufacture.