Flavonoids inhibit both rice and sheep serotonin N-acetyltransferases and reduce melatonin levels in plants

The plant melatonin biosynthetic pathway has been well characterized, but inhibitors of melatonin synthesis have not been well studied. Here, we found that flavonoids potently inhibited plant melatonin synthesis. For example, flavonoids including morin and myricetin significantly inhibited purified, recombinant sheep serotonin N-acetyltransferase (SNAT). Flavonoids also dose-dependently and potently inhibited purified rice SNAT1 and SNAT2. Thus, myricetin (100 μmol/L) reduced rice SNAT1 and SNAT2 activity 7- and 10-fold, respectively, and also strongly inhibited the N-acetylserotonin methyltransferase activity of purified, recombinant rice caffeic acid O-methyltransferase. To explore the in vivo effects, rice leaves were treated with flavonoids and then cadmium. Flavonoid-treated leaves had lower melatonin levels than the untreated control. To explore the direct roles of flavonoids in melatonin biosynthesis, we first functionally characterized a putative rice flavonol synthase (FLS) in vitro and generated flavonoid-rich transgenic rice plants that overexpressed FLS. Such plants produced more flavonoids but less melatonin than the wild-type, which suggests that flavonoids indeed inhibit plant melatonin biosynthesis.