title: Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans 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 (5) overproduced by an engineered strain of Aspergillus nidulans. The inhibitory activities of the semisynthetic azaphilones against 15-lipoxygenase were evaluated with several compounds displaying low micromolar potency.
authors.affiliation: Department of Chemistry, University of Southern California, College of Letters, Arts and Sciences, Los Angeles, California 90089, USA.
authors.forename: Amber D
authors.initials: AD
authors.lastname: Somoza
authors.forename: Kuan-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Chiang
authors.forename: Berl R
authors.initials: BR
authors.lastname: Oakley
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001233:Aspergillus nidulans / Q000737:chemistry / Q000378:metabolism*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D060847:Metabolic Engineering; D015394:Molecular Structure; D010860:Pigments, Biological / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D001688:Biological Products; D016859:Lipoxygenase Inhibitors; D010860:Pigments, Biological; C494154:azaphilone; D001093:Arachidonate 15-Lipoxygenase