Key advances in biocatalytic phosphorylations in the last two decades: Biocatalytic syntheses in vitro and biotransformations in vivo (in humans)

Biocatalytic phosphorylation reactions provide several benefits, such as more direct, milder, more selective, and shorter access routes to phosphorylated products. Favorable characteristics of biocatalytic methodologies represent advantages for in vitro as well as for in vivo phosphorylation reactions, leading to important advances in the science of synthesis towards bioactive phosphorylated compounds in various areas. The scope of this review covers key advances of biocatalytic phosphorylation reactions over the last two decades, for biocatalytic syntheses in vitro and for biotransformations in vivo (in humans). From the origins of probiotic life to in vitro synthetic applications and in vivo formation of bioactive pharmaceuticals, the common purpose is to outline the importance, relevance, and underlying connections of biocatalytic phosphorylations of small molecules. Asymmetric phosphorylations attracting increased attention are highlighted. Phosphohydrolases, phosphotransferases, phosphorylases, phosphomutases, and other enzymes involved in phosphorus chemistry provide powerful toolboxes for resource‐efficient and selective in vitro biocatalytic syntheses of phosphorylated metabolites, chiral building blocks, pharmaceuticals as well as in vivo enzymatic formation of biologically active forms of pharmaceuticals. Nature's large diversity of phosphoryl‐group‐transferring enzymes, advanced enzyme and reaction engineering toolboxes make biocatalytic asymmetric phosphorylations using enzymes a powerful and privileged phosphorylation methodology.