Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Sanya Institute of Oceanology, SCSIO, Yazhou Scientific Bay, Sanya 572000, China.
J Org Chem. 2021 Aug 20;86(16):11019-11028. doi: 10.1021/acs.joc.0c02517. Epub 2021 Feb 3.
Inactivation of the flavoenzyme-encoding gene in fluostatin biosynthesis led to the isolation of four new angucyclinone derivatives (, , , and ), among which fluostarenes A () and B () featured the unprecedented 6/6/5/6/6 pentacyclic skeleton with fusion of a benzo[]fluorene and a six-membered lactone ring. Both and were putatively generated via quinone methide-mediated nonenzymatic reactions. Fluostarene B () exhibited cytotoxicity against several cancer cell lines with IC values ranging from 7 to 10 μM. Fluostarenes A (), B (), and PK1 () showed α-glucosidase inhibition activity with IC of 0.89, 1.58, and 0.13 μM, respectively. Successful complementation of the Δ mutant with from kinamycin biosynthesis suggests that FlsO1 should function equivalently to AlpK as a putative C-5 hydroxylase.
在 fluostatin 生物合成中，对黄素酶编码基因的失活导致了四个新的蒽环酮衍生物（、、、和）的分离，其中 fluostarenes A () 和 B () 具有前所未有的 6/6/5/6/6 五环骨架，融合了苯并[]芴和六元内酯环。和都被推测是通过醌甲介导的非酶反应生成的。Fluostarene B () 对几种癌细胞系表现出细胞毒性，IC 值范围为 7 到 10 μM。Fluostarenes A ()、B () 和 PK1 () 对 α-葡萄糖苷酶的抑制活性的 IC 分别为 0.89、1.58 和 0.13 μM。用来自 kinamycin 生物合成的基因成功地互补 Δ突变体表明，FlsO1 应该与 AlpK 一样作为一个潜在的 C-5 羟化酶发挥作用。
