Reengineering an Azaphilone Biosynthesis Pathway in <i>Aspergillus nidulans</i> To Create Lipoxygenase Inhibitors

Abstract

Sclerotiorin, an azaphilone polyketide, is a bioactive natural product known to inhibit 15-lipoxygenase and many other biological targets. To readily access sclerotiorin and analogs, we developed a 2–3 step semisynthetic route to produce a variety of azaphilones starting from an advanced, putative azaphilone intermediate (<b>5</b>) overproduced by an engineered strain of <i>Aspergillus nidulans</i>. The inhibitory activities of the semisynthetic azaphilones against 15-lipoxygenase were evaluated with several compounds displaying low micromolar potency