4-hydroxy-2-pyrone formation by chalcone and stilbene synthase with nonphysiological substrates

Valerophenone synthase (VPS) is a polyketide synthase that catalyzes the fo rmation of the phloroglucinol derivatives in the synthesis of the bitter ac ids in hop (Humulus lupulus). The reaction uses isovaleryl-CoA or isobutyry l-CoA, but otherwise it is identical to that of the chalcone synthase in fl avonoid biosynthesis. Our study showed that chalcone synthase can perform t he function of VPS, but not perfectly, because the majority of the reaction s terminated after two condensation reactions (products: 4-hydroxy-2-pyrone derivatives). The same experiments with stilbene synthase yielded exclusiv ely the 4-hydroxy-2-pyrone derivatives, not the products expected from thre e condensation reactions. The results are discussed in the context of the f unctional diversity and evolution in the family of CHS-related polyketide s ynthases. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.