Discovery and Heterologous Production of Tetrapetalones Provide Insights into the Formation of the Tetracyclic System,Journal of Natural Products

当前位置： X-MOL 学术 › J. Nat. Prod. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Discovery and Heterologous Production of Tetrapetalones Provide Insights into the Formation of the Tetracyclic System
Journal of Natural Products ( IF 3.3 ) Pub Date : 2024-01-03 , DOI: 10.1021/acs.jnatprod.3c00813
Peng Shi ₁ , Yu Wang ₁ , Mengyujie Liu ₂ , Yaoyao Li ₂ , Jing Zhu ₁ , Yuemao Shen ₂ , Haoxin Wang ₁

Affiliation

Tetrapetalones make up a unique class of pentaketide ansamycins that feature a tetracyclic skeleton and exhibit potent inhibitory activities against soybean lipoxygenase. However, a detailed biosynthetic route to tetrapetalones has not been published. Herein we report the activation of the tetrapetalones’ biosynthetic gene cluster (tpt) in Streptomyces sp. S10 by promoter engineering along with constitutive expression of pathway-specific regulator genes, leading to the discovery of seven new derivatives, tetrapetalones E–K (2–8), and the known tetrapetalone A (1). In vivo gene deletion experiments and heterologous expression of the minimized tpt cluster in Streptomyces albus J1074 suggest that the tetracyclic system of tetrapetalones is probably formed spontaneously, and the regioselective glycosylation of tetrapetalones at the C-9 hydroxy group with d-rhamnose or d-rhodinose was catalyzed by the glycosyltransferase Tpt14.

中文翻译：

四酮的发现和异源生产为四环系统的形成提供了见解

四酮是一类独特的五肽安沙霉素，具有四环骨架，对大豆脂氧合酶表现出有效的抑制活性。然而，四酮酮的详细生物合成路线尚未公布。在此，我们报告了链霉菌中四瓣酮生物合成基因簇（ tpt ）的激活。 S10 通过启动子工程以及途径特异性调节基因的组成型表达，导致七种新衍生物的发现，即四酮 E–K ( 2 – 8 ) 和已知的四酮 A ( 1 )。白色链霉菌J1074 中最小化tpt簇的体内基因缺失实验和异源表达表明，四瓣酮的四环系统可能是自发形成的，并且四瓣酮在 C-9 羟基上与d-鼠李糖或d-铑丁糖发生区域选择性糖基化。由糖基转移酶 Tpt14 催化。

更新日期：2024-01-03

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南