ABSTRACT
Redox tailoring enzymes play key roles in generating structural complexity and diversity in typeâ II polyketides. In chartreusin biosynthesis, the early 13 C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the α-pyrone containing pentacyclic intermediate in an NADPH-dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous γ-lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide.
ABSTRACT
Two new 2-carboxymethyl-3-hexyl-maleic anhydride derivatives, arthrianhydride A (1) and B (2), along with three known compounds 3-5, were isolated from the fermentation broth of a grasshopper-associated fungus Arthrinium sp. NF2410. The structures of new compounds 1 and 2 were determined based on the analysis of the HR-ESI-MS and NMR spectroscopic data. Furthermore, compounds 1 and 2 were evaluated on inhibitory activity against the enzyme SHP2 and both of them showed moderate inhibitory activity against SHP2.
Subject(s)
Anhydrides/pharmacology , Enzyme Inhibitors/pharmacology , Fungi/chemistry , Grasshoppers/microbiology , Anhydrides/isolation & purification , Animals , Biological Products/isolation & purification , Biological Products/pharmacology , Enzyme Inhibitors/isolation & purification , Molecular Structure , Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & inhibitors , Secondary MetabolismABSTRACT
The mangrove-derived endophytic fungus Peniophora incarnata Z4 produced seven new xanthone derivatives, including four new tetrahydroxanthones (1-4), one new chromone (5), one new xanthone (6), and one new xanthone dimer (7), together with one known compound, globosuxanthone B (8). Their structures were determined by an extensive analysis of 1D and 2D NMR, HRESIMS, ECD, and single-crystal X-ray diffraction data. In cytotoxic activity assays, compound 2 showed cytotoxicity against three carcinoma cell lines with IC50 values less than 10 µM.
