Chemoenzymatic Synthesis Of C₁₀-Isopentenyl Chalcon

Chalcones are 1,3-diaryl-2-propen-1-ones,where rings A and B are joined by a three carbon unsaturated carbonyl bridge.As an important branch of chalcone compounds,prenylated chalcone is modified by C₅-,C₁₀-,C₁₅-,or C₂₀-prenyl group at both rings orα,β-carbons,which often increases the lipophilicity of the backbone compounds and leads to enhancement of their affinity for proteins and cell membranes and therefore biological activities,and geranylated chalcone has antioxidant,antitumor,inhibitsα-glucosidase,etc.There are many ways to obtain these compounds,such as plant and chemical synthesis sources,but enzyme synthesis has become one of the research hotspots because of its high efficiency and green characteristics.Geranylated chalcones mainly exist in plants and many of them have attracted attention because of their diverse pharmacological and biological activities.Herein,we report geranylation of ten chalcones by the fungi aromatic prenyltransferases AtaPT and AnaPT.Sixteen geranylated chalcones were identified,of which twelve mono-geranylated enzyme products（1G-6G,7G1,7G2,8G,9G1,9G2,and 10G3）were new products.Most of products are C-geranylated products with geranyl moieties at ring B.In comparison,plant aromatic prenyltransferases usually catalyze compounds 1,and 2at ring A according to reports in literature.Therefore,AtaPT can be used complementarily for geranylation of chalcone 1,and 2 to increase structural diversity of small molecules.Enzymatic kinetic parameter tests revealed that 1 was the most efficiently accepted by AtaPT in the presence of GPP with a k_cat/K_M value of 1666.7 s^-1M^-1,followed by 2 with a k_cat/K_M value of 1083.3 s^-1M^-1.AtaPT displayed similar catalytic efficiency to 3-5 with k_cat/K_M values of between 522 and 722.2 s^-1M^-1,respectively.Lower catalytic efficiencies with k_cat/K_M values ranging from 200.0 to350.0 s^-1M^-1were determined for 6-9.In addition,eight compounds（1G,3G,4G,5G,7G1,8G,9G1,and 9G1）exhibited potential inhibitory effect onα-glucosidase with the IC₅₀values ranging from 45.59±3.48 to 82.85±2.15μg/m L.Among them,compound8G（45.59±3.48μg/m L）was the most potentialα-glucosidase inhibitor,which is about seven times stronger than the positive control,acarbose(IC₅₀=346.63±15.65μg/m L).The above eight compounds have weak antioxidant activity,with an inhibition rate of13%-43%,of which 1G（43.3%）has potential antioxidant activity.