"The more we recycle, the less we need to mine." -Wilfred Visser Despite the impressive biocatalytic synthesis routes that have been developed in recent decades (and that have also found application in industry), there are still prejudices against enzymatic catalysts. This is often due to observed or perceived instabilities (to temperature, pH, cosolvents or shearing forces), the relatively high price of enzymes, or their limited reusability compared to organo-catalysts or transition metals. While the use of thermostable nucleoside phosphorylases resolves many of the stability issues classically associated with enzymes, such as resistance to high temperatures or cosolvent contents, immobilization approaches typically grant further stability and enable a reuse, ultimately resulting in a drastic reduction of overall cost. In the field of nucleoside biocatalysis, enzymes have primarily been immobilized by binding to an ion exchange resin or by covalent binding to a solid support. Indeed, the use of such classically immobilized nucleoside phosphorylases in flow reactors has been demonstrated in several proof-of-concept studies for the synthesis of pyrimidine and purine nucleosides. However, due to persistent drawbacks (primarily costly resins as well as large losses of enzyme activity by immobilization), several alternative immobilization techniques have been developed in recent years. For instance, the covalent but reversible immobilization of a purine nucleoside phosphorylase on agarose microbeads activated with thiol groups allowed a recycling of the resin after the enzyme was inactivated. In a different approach, cross-linking based selfimmobilization of Escherichia coli uridine phosphorylase even eliminated the need for an external support. Building on the early advances in enzyme immobilization, the past decade has seen the emergence of in situ immobilization as a viable alternative to classical approaches. In situ immobilization typically provides a much smoother and simpler purification process and retains higher activities compared to classical methods. Among the different approaches (see e.g. the review by Rehm and colleagues), inclusion body-based approaches have recently attracted the most attention. Although inclusion bodies are relatively heterogenous in their composition and typically occur as undesired side products during protein expression, they can preserve enzymatic activity and act as biological solid supports. The formation of such catalytically active inclusion bodies is typically induced by the addition of specific aggregation-supporting tags to the target protein, although naturally occurring catalytically active inclusion bodies may also exist. Recently, several suitable tags have been identified which induce the formation of such inclusion bodies and their application to a variety of different proteins has been shown. Notably, a very recent study from the Krauss group 46 demonstrated the robust use of catalytically active inclusion bodies in flow chemistry which is an important step towards their wide-spread application. Although such engineered inclusion bodies have not been used in the field of nucleoside synthesis so far, we believe that they offer a valuable alternative to the use of purified or classically immobilized enzymes. However, their successful implementation in synthetic processes will require a union of biochemistry and flow technology.