异源表达 II 型 PKS 基因簇导致 J1074 中产生多样化的安卡环素类化合物。

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

机构信息

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China.

出版信息

Mar Drugs. 2024 Oct 22;22(11):480. doi: 10.3390/md22110480.

DOI:10.3390/md22110480

PMID:39590760

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11595736/

Abstract

Heterologous expression has emerged as an effective strategy in activating cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster derived from marine sp. HDN155000 in the chassis host 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 () contains a rare thiomethyl group, angumycinone T () has a novel oxo-bridge formed between C12a and C4, and angumycinone X () showed cytotoxicity toward K562 and NCI-H446/EP cell lines.

摘要

异源表达已成为激活隐性基因簇或提高产量的有效策略。通过在底盘宿主 J1074 中异源表达海洋 sp. HDN155000 的 II 型 PKS 基因簇，成功获得了 8 种化合物。通过广泛的 MS 和 NMR 光谱方法以及理论 NMR 计算和电子圆二色性 (ECD) 计算，阐明了具有绝对构型的结构。有趣的是，化合物 WS009 Z () 含有一个罕见的硫甲基，angumycinone T () 在 C12a 和 C4 之间形成了一个新的氧桥，而 angumycinone X () 对 K562 和 NCI-H446/EP 细胞系表现出细胞毒性。