Engineering Yeast for Production of Benzophenones and Xanthones as Precursors of Polycyclic Polyprenylated Acylphloroglucinols

Polycyclic polyprenylated acylphloroglucinols (PPAPs) exhibit a broad range of biological activities, such as antidepressant, antibacterial, antiviral and antitumor properties. The content of PPAPs in the producing plants is often quite low, and their complex structures make total chemical synthesis difficult and economically impractical. Progresses in synthetic biology provide an alternative approach for the production of these valuable compounds. Here we present our results on reconstruction of the biosynthetic pathways of PPAP precursors in yeast. Based on our previous works on the biosynthesis of PPAPs, genes involved in the formation of benzophenones and xanthones from Hypericum sp. and other organisms were expressed in yeast either episomally or by integration into the genome. The production of the expected products reached around 0.5 mg/l, which is high enough to be the substrate for enzymes of subsequent biosynthetic steps. The yeast strains will be further engineered by introducing various prenyltransferase enzymes to reconstruct the full biosynthetic pathways of PPAPs.