Discovery of Prenyltransferase-Guided Hydroxyphenylacetic Acid Derivatives from Marine Fungus sp. W21C371.

Traditional isolation methods often lead to the rediscovery of known natural products. In contrast, genome mining strategies are considered effective for the continual discovery of new natural products. In this study, we discovered a unique prenyltransferase (PT) through genome mining, capable of catalyzing the transfer of a prenyl group to an aromatic nucleus to form C-C or C-O bonds. A pair of new hydroxyphenylacetic acid derivative enantiomers with prenyl units, (±)-peniprenydiol A (), along with 16 known compounds (-), were isolated from a marine fungus, sp. W21C371. The separation of using chiral HPLC led to the isolation of the enantiomers and . Their structures were established on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS. The absolute configurations of the new compounds were determined by a modified Mosher method. A plausible biosynthetic pathway for was deduced, facilitated by PT catalysis. In the in vitro assay, and showed promising inhibitory activity against -glucuronidase (EcGUS), with IC values of 44.60 ± 0.84 μM and 21.60 ± 0.76 μM, respectively, compared to the positive control, -saccharic acid 1,4-lactone hydrate (DSL). This study demonstrates the advantages of genome mining in the rational acquisition of new natural products.