Benzalacetone synthase

Benzalacetone synthase (BSA) is a novel plant‐specific polyketide synthase that catalyzes a one step decarboxylative condensation of 4‐coumaroyl‐CoA with malonyl‐CoA to produce the C 6 –C 4 skeleton of phenylbutanoids in higher plants. A cDNA encoding BAS was for the first time cloned and sequenced from rhubarb ( Rheum palmatum ), a medicinal plant rich in phenylbutanoids including pharmaceutically important phenylbutanone glucoside, lindleyin. The cDNA encoded a 42‐kDa protein that shares 60–75% amino‐acid sequence identity with other members of the CHS‐superfamily enzymes. Interestingly, R. palmatum BAS lacks the active‐site Phe215 residue (numbering in CHS) which has been proposed to help orient substrates and intermediates during the sequential condensation of 4‐coumaroyl‐CoA with malonyl‐CoA in CHS. On the other hand, the catalytic cysteine‐histidine dyad (Cys164–His303) in CHS is well conserved in BAS. A recombinant enzyme expressed in Escherichia coli efficiently afforded benzalacetone as a single product from 4‐coumaroyl‐CoA and malonyl‐CoA. Further, in contrast with CHS that showed broad substrate specificity toward aliphatic CoA esters, BAS did not accept hexanoyl‐CoA, isobutyryl‐CoA, isovaleryl‐CoA, and acetyl‐CoA as a substrate. Finally, besides the phenylbutanones in rhubarb, BAS has been proposed to play a crucial role for the construction of the C 6 –C 4 moiety of a variety of natural products such as medicinally important gingerols in ginger plant.