AbstractBioreactors are the operative backbone, for example, for the production of biopharmaceuticals, biomaterials in tissue engineering, and sustainable substitutes for chemicals. Still, the Achilles' heel of bioreactors nowadays is the aeration which is based on intense stirring and gas sparging, yielding inherent drawbacks such as shear stress, foaming, and sterility concerns. We present the synergistic combination of simulations and experiments toward a membrane stirrer for the efficient bubble‐free aeration of bioreactors. A digital twin of the bioreactor with an integrated membrane‐module stirrer (MemStir) was developed with computational fluid dynamics (CFD) studies addressing the determination of fluid mixing, shear rates, and local oxygen concentration. Usability of the MemStir is shown in a foam‐free recombinant production process of biosurfactants (rhamnolipids) from glucose with different strains ofPseudomonas putidaKT2440 in a 3‐L vessel and benchmarked against a regular aerated process. The MemStir delivered a maximal oxygen transfer rate (OTR_max) of 175 mmol L⁻¹h⁻¹in completely foam‐free cultivations. With a high space‐time yield (STY) of 118 mg_RLL⁻¹h⁻¹during a fed‐batch fermentation, the effectiveness of the novel MemStir is demonstrated. Simulations show the generic value of the MemStir beyond biosurfactant production, for example, for animal cell cultivation.