In the last years, there were two fields that experienced an astonishing growth within the biocatalysis community: photobiocatalysis and applications of flow technology to catalytic processes. Therefore, it is not a surprise that the combination of these two research areas also gave place to several recent interesting articles. However, to the best of our knowledge, no review article covering these advances was published so far. Within this review, we present recent and very recent developments in the field of photobiocatalysis in continuous flow, we discuss several different practical applications and features of state-of-the art photobioreactors and lastly, we present some future perspectives in the field.

In recent years, 3D printing has emerged in the field of chemical engineering as a powerful manufacturing technique to rapidly design and produce tailor-made reaction equipment. In fact, reactors with complex internal geometries can be easily fabricated, optimized and interchanged in order to respond to precise process needs, such as improved mixing and increased surface area. These advantages make them interesting especially for catalytic applications, since customized structured bed reactors can be easily produced. 3D printing applications are not limited to reactor design, it is also possible to realize functional low cost alternatives to analytical equipment that can be used to increase the level of process understanding while keeping the investment costs low. In this work, in-house designed ceramic structured inserts printed via vat photopolymerization (VPP) are presented and characterized. The flow behavior inside these inserts was determined with residence time distribution (RTD) experiments enabled by in-house designed and 3D printed inline photometric flow cells. As a proof of concept, these structured inserts were fitted in an HPLC column to serve as solid inorganic supports for the immobilization of the enzyme Phenolic acid Decarboxylase (bsPAD), which catalyzes the decarboxylation of cinnamic acids. The conversion of coumaric acid to vinylphenol was chosen as a model system to prove the implementation of these engineered inserts in a continuous biocatalytic application with high product yield and process stability. The setup was further automated in order to quickly identify the optimum operating conditions via a Design of Experiments (DoE) approach. The use of a systematic optimization, together with the adaptability of 3D printed equipment to the process requirements, render the presented approach highly promising for a more feasible implementation of biocatalysts in continuous industrial processes.

Advances in flow chemistry to produce active pharmaceutical ingredients (APIs) require performing reactions in tailor-made equipment as complexity of the planned setups increases. To react quickly and with low costs to these demanding reactions, additive manufacturing, also known as 3D printing, is a preferred way for the production of customized reactors. This work presents three examples of 3D printed reactors and their application for the synthesis of API precursors in continuous flow. The first case deals with an aerobic oxidation of Grignard reagents to the corresponding phenols by molecular oxygen. Here, a design concept was utilized; various stainless steel reactors were tested, and their performances were evaluated in continuous flow. Next, another stainless steel reactor was applied for achieving fast mixing in a cascade, leading to a valsartan precursor. The third and final case employed a continuous stirred tank reactor (CSTR) made of a UV-curable resin. It was used for the first step of a multiphase enzymatic decarboxylation followed by a Heck cross-coupling reaction, leading to resveratrol derivatives.

Photo‐ and biocatalysis show many advantages as more sustainable solutions for the production of fine chemicals. In an effort to combine the benefits and the knowledge of both these areas, a continuous photobiocatalytic setup was designed and optimized to carry out whole‐cell biotransformations within cells of the cyanobacterium Synechocystis sp. PCC 6803 expressing the gene of the ene‐reductase YqjM from B. subtilis. The effect of the light intensity and flow rate on the specific activity in the stereoselective reduction of 2‐methyl maleimide was investigated via a design‐of‐experiments approach. The cell density in the setup was further increased at the optimal operating conditions without loss in specific activity, demonstrating that the higher surface area/volume ratio in the coil reactor improved the illumination efficiency of the process. Furthermore, different reactor designs were compared, proving that the presented approach was the most cost‐ and time‐effective solution for intensifying photobiotransformations within cyanobacterial cells.