Tetrahydroxanthone
Tetrahydroxanthones are natural products formally derived by partial reduction of xanthone. They are produced by various fungi, bacteria, and plants. Some are precursors to larger xanthone natural products. One example is neosartorin, composed of 5-acetylblennolide A and blennolide C, exhibits antibacterial activity against Gram-positive bacteria, notably including "Staphylococcus aureus". Chrysophanol is the common intermediate to most if not all tetrahydroxanthones. The "nsr cluster" is a polyketide synthase gene responsible for the biosynthesis of neosartorin in "A. novofumigatus". The enzyme "NsrQ" features a catalytic glutamic acid residue in the active site which protonates the enol produced by "NsrK , leading to dearomatization. The biosynthesis of tetrahydroxanthones begins with the synthesis of the anthraquinone chrysophanol (see figure). Once the final reduction and dehydration events take place (NsrJ" and "NsrI"), chrysophanol is accepted into monooxygenase "NsrF". A ring opening occurs upon the addition of water to the "NsrF" product 8 to give 9. "NsrG", a methyltransferase, then converts the carboxylic acid into an ester, giving 10 as the product. "NsrK", a flavin-dependent monooxygenase, the installs an alcohol "ortho"- to the ester and methyl groups, breaking the aromaticity of the compound. "NsrQ," an NADPH dependent ketoreductase, then isomerizes the methyl group  to form 12 and 14. The two isomers are then acted upon by either "NsrO" and "CPUR_05418" or just "NsrO" to give (-)-blennolide B and blennolide A. Further transformation of blennolide A by "NsrL" yields the precursor natural product 5-actelyblennolide A.