In this work, we have shown how polymer conformational changes regulated by a fuel-driven esterification CRN can induce transient colloidal depletion aggregation. Upon acetylation by a chemical fuel, the polymer undergoes a temporal transition from a random coil to a compact globule. In the random coil conformation it acts as a polymeric depletant for silica colloids, while in its globular form it is too small to act as depletant for this system. Later in the fuel cycle the polymer is deacetylated again, reobtaining its depletion capacity. The concept was visualized using optical microscopy. The colloidal clusters are fractal-like structures due to the existence of a secondary minimum and the colloids remain dynamic over the course of the fuel cycle. Overall, a fuel cycle initiated by the addition of chemical fuel on the molecular scale results in a microscopic response with a transient colloidal depletion cycle and thus provides a temporary way out of thermodynamic equilibrium on large length scales. Understanding the propagation from a molecular reaction network to the microscopic or even macroscopic world is important for further research in this field and can support the design of responsive materials with life-like properties.