Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
Institute of Marine Science and Technology, Shandong University, Qingdao 266237, China.
J Nat Prod. 2021 Nov 26;84(11):2875-2884. doi: 10.1021/acs.jnatprod.1c00617. Epub 2021 Nov 16.
Angucyclines and angucyclinones are aromatic polyketides with intriguing structures and therapeutic value. Genome mining of the rare marine actinomycete sp. D09 led to the identification of a type II polyketide synthase biosynthetic gene cluster, , which encodes several distinct subclasses of oxidoreductases, implying that this strain has the potential to produce novel polycyclic aromatic polyketides with unusual redox modifications. The "one strain-many compounds" (OSMAC) strategy and comparative metabolite analysis facilitated the discovery of 20 angucycline derivatives from the D09 strain, including six new highly oxygenated saccharothrixins D-I (-), four new glycosylated saccharothrixins J-M (-), and 10 known analogues (-). Their structures were elucidated based on detailed HRESIMS, NMR spectroscopic, and X-ray crystallographic analysis. With the help of gene disruption and heterologous expression, we proposed their plausible biosynthetic pathways. In addition, compounds , , and showed antibacterial activity against with MIC values ranging from 16 to 32 μg/mL. Compound also revealed anti-inflammatory activity by inhibiting the production of NO with an IC value of 28 μM.
蒽环类和蒽环酮是具有有趣结构和治疗价值的芳族聚酮。稀有海洋放线菌 sp. D09 的基因组挖掘导致了鉴定出一个 II 型聚酮合酶生物合成基因簇，该基因簇编码几种不同类别的氧化还原酶，这意味着该菌株有可能产生具有不寻常氧化还原修饰的新型多环芳烃聚酮。“一种菌株-多种化合物”（OSMAC）策略和比较代谢物分析有助于从 D09 菌株中发现 20 种蒽环类衍生物，包括 6 种新型高度氧化的 saccharothrixin D-I (-)，4 种新型糖基化 saccharothrixin J-M (-)，和 10 种已知类似物 (-)。它们的结构是基于详细的 HRESIMS、NMR 光谱和 X 射线晶体学分析来阐明的。在基因敲除和异源表达的帮助下，我们提出了它们可能的生物合成途径。此外，化合物 、 和 对 显示出抗菌活性，MIC 值范围为 16-32 μg/mL。化合物 还通过抑制 NO 的产生显示出抗炎活性，IC 值为 28 μM。
