This article aims to develop a method to automatically generate CFD-based compartment models. This effort to simplify mixing models aims at capturing the interactions between material transport and chemical/biochemical conversions in large-scale reactors. The proposed method converts the CFD results into a system of mass balance equations for each defined component. The compartmentalization method is applied to two bioreactor geometries and was able to replicate tracer mixing profiles observed in CFD simulations. The generated compartment models were successfully coupled with, a simple Monod-type biokinetic model describing microbial growth, substrate consumption and product formation. The coupled model was used to simulate a four-hour fermentation in a 190 L reactor and a 10 m3 reactor. Resolving the substrate gradients had a clear impact on the biokinetics, increasing with the scale of the reactor. Moreover, the coupled model could simulate the fermentation faster than real-time. Having a real-time-solvable model is essential for implementations in digital twins and other real-time applications using the models as predictive tools.