Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.
Momomycin, an Antiproliferative Cryptic Metabolite from the Oxytetracycline Producer Streptomyces rimosus.
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DOI：
10.1002/anie.202208573
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发表时间：
2022-09-26
影响因子：
16.6
通讯作者：
Seyedsayamdost, Mohammad R.
中科院分区：
文献类型：
--
作者：
Li, Yuchen;Lee, Seoung Rak;Han, Esther J.;Seyedsayamdost, Mohammad R.
天然产物是药物和化学工具的重要来源。传统上，对未开发的微生物门的评估导致了新的天然产物。然而，随着每一种新的微生物的出现，孤儿生物合成基因簇（BGC）的数量也在增加。因此，更困难的问题是从经过充分研究的菌株中找到新的分子。在此，我们以广泛使用的土霉素生产者链霉菌（Streptomyces rimosus）为目标，发现新的天然产物。利用maldi - ms引导的高通量启动子筛选（HiTES），我们绘制了S. rimosus的全球次级代谢组和三种隐型bgc的结构特征产物，包括momomycin，一种不寻常的环状肽天然产物，具有骨干修饰和几种非规范氨基酸。介绍了其生物合成的重要方面，并对其生物活性进行了评价。我们的研究表明，HiTES是一种从“排水”菌株中发掘新化学物质的有效方法。微生物制药商仍在为数十种尚未鉴定的天然产品编码。本文采用高通量激发子筛选方法，从土霉素的工业生产者链霉菌（Streptomyces rimosus）中发现了三组隐代代谢物，特别是momomycin，一种具有抗增殖特性的新型环状肽。
Natural products provide an important source of pharmaceuticals and chemical tools. Traditionally, assessment of unexplored microbial phyla has led to new natural products. However, with every new microbe, the number of orphan biosynthetic gene clusters (BGC) grows. As such, the more difficult proposition is finding new molecules from well-studied strains. Herein, we targeted Streptomyces rimosus, the widely-used oxytetracycline producer, for the discovery of new natural products. Using MALDI-MS-guided high-throughput elicitor screening (HiTES), we mapped the global secondary metabolome of S. rimosus and structurally characterized products of three cryptic BGCs, including momomycin, an unusual cyclic peptide natural product with backbone modifications and several non-canonical amino acids. We elucidated important aspects of its biosynthesis and evaluated its bioactivity. Our studies showcase HiTES as an effective approach for unearthing new chemical matter from “drained” strains. Microbial producers of pharmaceuticals still code for dozens of yet-to-be identified natural products. Herein, three groups of cryptic metabolites were uncovered from Streptomyces rimosus, the industrial producer of oxytetracycline, using high-throughput elicitor screening, notably momomycin, a novel cyclic peptide with antiproliferative properties.
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DOI：
10.1073/pnas.1008368107
发表时间：
2010-09-14
影响因子：
11.1
作者：
Liu, Wei-Ting;Yang, Yu-Liang;Dorrestein, Pieter C.
通讯作者：
Dorrestein, Pieter C.
影响因子：
--
作者：
Kobylarz, Marek J.;Grigg, Jason C.;Murphy, Michael E. P.
通讯作者：
Murphy, Michael E. P.
影响因子：
3.6
作者：
Matsumori, N;Kaneno, D;Tachibana, K
通讯作者：
Tachibana, K
影响因子：
7.4
作者：
Fujii, K;Ikai, Y;Harada, K
通讯作者：
Harada, K
影响因子：
4
作者：
Covington BC;Seyedsayamdost MR
通讯作者：
Seyedsayamdost MR