Activity of 6-hydroxymellein synthase, an induced polyketide synthetic
enzyme in carrot cell extract, was not inhibited by cerulenin which i
s known as a potent inhibitor for fatty acid synthases and biosyntheti
c enzymes of various polyketide compounds. However, when 6-hydroxymell
ein synthase was incubated with [H-3]cerulenin in the absence of its s
ubstrates, acyl-CoAs, significant radioactivity was found to co-migrat
e with the enzyme protein in SDS-PAGE analysis. The radioactivity asso
ciated with the synthase was not observed when the cerulenin-enzyme co
mplex was post-incubated with acyl-CoAs. These results suggest that ce
rulenin is able to bind to 6-hydroxymellein synthase and forms a compl
ex. However, the attachment is unstable and the substrates of the synt
hase are capable of replacing the inhibitor at the reaction centre.