On December 12, 2016, Natural chemical biology reported a new research progress entitled Molecular Insights Into The Enzyme Promiscuity Of An Aromatic Prenyltransferase by Chinese Academy of Medical Sciences and Peking Union Medical College and Institute of Biophysics, Chinese Academy of Sciences. They reported a new type of aromatic prenyltransferase (AtaPT) that is cloned from microorganism with unprecedented substrate promiscuity, and discovered the relevant molecular mechanism.  

Traditionally, enzymes are considered to be specific towards their substrates; however, many enzymes show substrate promiscuity, which is different from natural substrates. The promiscuity of enzymes has draw people’s attraction, but the molecular mechanism is still unclear.  

The substitution reactions of prenyl moieties on natural compounds give rise to kinds of products with variety of structural types and bioactivities, which are important source for new drug discovery. The introduction of prenyl moieties into natural molecules enriches the diversity of structural types greatly, and enhances the bioactivities by increasing the lipophilic properties. Thus, an aromatic prenyltransferase with diverse substrate is an important tool for drug discovery.  

In their research, a brand new prenyltransferase gene named AtaPT was discovered, and the recombinant protein AtaPT could not only accept donors with different chain length (C_5,C_10,C_15,C₂₀), but also different kinds of acceptors, including genestins, cycled-L-Trp, quinoline alkaloids, xanthone, dimethyl ketone, flavonoids and so on with high efficiency and many kinds of substitution reaction (O-、C-prenylation), showing great substrate promiscuity never reported before (Fig. 1).