白链霉菌 J1074 中 II 型 PKS 基因簇的异源表达可产生多样化的血管环素。

IF 4.9 2区医学 Q1 CHEMISTRY, MEDICINAL

Marine Drugs Pub Date : 2024-10-22 DOI:10.3390/md22110480

Xiaoting Zhang, Falei Zhang, Chen Li, Jiayi Li, Xiao Xu, Tianjiao Zhu, Qian Che, Deihai Li, Guojian Zhang

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引用次数: 0

摘要

异源表达已成为激活链霉菌隐性基因簇或提高产量的有效策略。通过在底盘宿主白链霉菌 J1074 中异源表达来自海洋链霉菌 HDN155000 的 II 型 PKS 基因簇 spi，成功获得了 8 种化合物。通过大量的 MS 和 NMR 光谱方法以及 NMR 理论计算和电子圆二色性（ECD）计算，阐明了这些化合物的绝对构型结构。有趣的是，化合物 WS009 Z (2) 含有一个罕见的硫代甲基，安格霉素酮 T (4) 的 C12a 和 C4 之间形成了一个新颖的氧化桥，安格霉素酮 X (3) 对 K562 和 NCI-H446/EP 细胞株具有细胞毒性。

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Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074.

Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.

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来源期刊

Marine Drugs 医学-医药化学

CiteScore

9.60

自引率

14.80%

发文量

671

审稿时长

1 months

期刊介绍： Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.