Organic chemistry is continually evolving to improve the syntheses of value added and bioactive compounds. Through this progression, a concomitant advancement in laboratory technology has occurred. Many researchers now choose to mediate transformations in continuous-flow systems given the many benefits over round bottom flasks. Furthermore, reaction scale up is often less problematic as this is addressed at the inception of the science. Although single-step transformations in continuous-flow systems are common, multi-step transformations are more valuable. In these systems, molecular complexity is accrued through sequential transformations to a mobile scaffold, much like an in vitro version of Nature's polyketide synthases. Utilizing this methodology, multi-step continuous-flow systems have improved the syntheses of active pharmaceutical ingredients (APIs), natural products, and commodity chemicals. This Review details these advancements while highlighting the rapid progress, benefits, and diversification of this expanding field.

The continuous flow synthesis of active pharmaceutical ingredients, value-added chemicals, and materials has grown tremendously over the past ten years. This revolution in chemical manufacturing has resulted from innovations in both new methodology and technology. This field, however, has been predominantly focused on synthetic organic chemistry, and the use of biocatalysts in continuous flow systems is only now becoming popular. Although immobilized enzymes and whole cells in batch systems are common, their continuous flow counterparts have grown rapidly over the past two years. With continuous flow systems offering improved mixing, mass transfer, thermal control, pressurized processing, decreased variation, automation, process analytical technology, and in-line purification, the combination of biocatalysis and flow chemistry opens powerful new process windows. This Review explores continuous flow biocatalysts with emphasis on new technology, enzymes, whole cells, co-factor recycling, and immobilization methods for the synthesis of pharmaceuticals, value-added chemicals, and materials.

Driving chemical transformations in dynamic thin films represents a rapidly thriving and diversifying research area. Dynamic thin films provide a number of benefits including large surface areas, high shearing rates, rapid heat and mass transfer, micromixing, and fluidic pressure waves. Combinations of these effects provide an avant-garde style of conducting chemical reactions with surprising and unusual outcomes. The vortex fluidic device (VFD) has proved its capabilities in accelerating and increasing the efficiencies of numerous organic, materials and biochemical reactions. This MiniReview surveys transformations that have benefited from VFD-mediated processing, and identifies concepts driving the effectiveness of vortex-based dynamic thin films.

Enzymes catalyze chemical transformations with outstanding stereo- and regio-specificities, but many enzymes are limited by their long reaction times. Here, we describe a general method to accelerate enzymes using pressure waves contained within thin films. Each enzyme responds best to specific frequencies of pressure waves, and we report acceleration landscapes for each protein. A vortex fluidic device introduces pressure waves that drive increased rate constants (kcat) and enzymatic efficiency (kcat/Km). Four enzymes displayed an average seven-fold acceleration with deoxyribose-5-phosphate aldolase (DERA) achieving an average 15-fold enhancement through this approach. In solving a common problem in enzyme catalysis, we have uncovered a powerful, generalizable tool for enzyme acceleration. This research provides new insights into previously uncontrolled factors affecting enzyme function.