传统的分离方法通常导致已知天然产物的重新发现。相比之下,基因组挖掘策略被认为对于不断发现新的天然产物是有效的。在这项研究中,我们通过基因组挖掘发现了一种独特的异戊烯基转移酶(PT),能够催化异戊二烯基转移到芳香核以形成C-C或C-O键。一对新的含异戊二烯基单元的羟基苯乙酸衍生物对映体,(±)-戊烯二醇A(1),连同16种已知化合物(2-17),是从一种海洋真菌中分离出来的,青霉。W21C371.使用手性HPLC分离1导致对映体1a和1b的分离。它们的结构是在广泛的光谱分析的基础上建立的,包括1D,2DNMR和HRESIMS。通过改进的Mosher方法确定新化合物的绝对构型。推导出1的一个合理的生物合成途径,由PT催化促进。在体外检测中,2和3显示了对大肠杆菌β-葡糖醛酸酶(EcGUS)的有希望的抑制活性,IC50值为44.60±0.84μM和21.60±0.76μM,分别,与阳性对照相比,D-糖精酸1,4-内酯水合物(DSL)。这项研究证明了基因组挖掘在合理获取新天然产物方面的优势。
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 (1), along with 16 known compounds (2-17), were isolated from a marine fungus, Penicillium sp. W21C371. The separation of 1 using chiral HPLC led to the isolation of the enantiomers 1a and 1b. 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 1 was deduced, facilitated by PT catalysis. In the in vitro assay, 2 and 3 showed promising inhibitory activity against Escherichia coli β-glucuronidase (EcGUS), with IC50 values of 44.60 ± 0.84 μM and 21.60 ± 0.76 μM, respectively, compared to the positive control, D-saccharic acid 1,4-lactone hydrate (DSL). This study demonstrates the advantages of genome mining in the rational acquisition of new natural products.