Making molecules with photodecarboxylases: a great start or a false dawn?

Photoenzymes are potentially attractive biocatalysts for chemicals synthesis and biomanufacturing. They do not require coenzymes such as NAD(P)H, or high energy molecules like ATP, and their activity can be controlled precisely in a temporal and spatial manner by light. The light-activated fatty acid photodecarboxylase (FAP) was discovered in 2017. Since its discovery, biophysical, structural, and computational methods have been used to understand how FAP uses blue light to catalyze the decarboxylation of fatty acid substrates. As a natural photobiocatalyst, FAP could offer insights into the design of new photoenzymes. Here, we provide a perspective on the structure, mechanism and biotechnological applications of FAP enzymes, and understanding from which new photobiocatalysts could be developed. We review early success in the engineering of FAPs but also identify major challenges for wider use of this recently discovered enzyme family in biotechnology and the chemical sciences. Based on these early insights, the reader is invited to consider if the use of FAPs will continue to flourish in biotechnology applications, or whether current known limitations signify a false dawn.