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The antitumor compound psymberin as a model to develop heterologous expression systems for polyketides from uncultivated sponge symbionts

抗肿瘤化合物 psymberin 作为开发未培养海绵共生体聚酮化合物异源表达系统的模型

基本信息

批准号：
161899924
负责人：
Professor Dr. Jörn Piel
金额：
--
依托单位：
Institut für Mikrobiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/161899924?language=en
关键词：
antitumor compound psymberin model develop

项目摘要

There is increasing evidence that many bioactive natural products isolated from marine sponges are synthesized by as-yet unculturable bacterial symbionts. However, the elusive lifestyle of these microbes has so far precluded the systematic exploration of their chemical and pharmacological potential. Our group has recently developed a suite of metagenomic techniques that demonstrated for the first time a bacterial origin for sponge-derived polyketides by providing access to the biosynthetic genes. Goal of the proposed work is to develop bacterial expression systems for symbiont genes that can be used to generate sustainable production sources of rare marine natural products. The model compound for these studies will be psymberin, a potent inhibitor of solid tumors isolated from the sponge Psammocinia aff. bulbosa. Using various preselected host strains, gene transfer systems and promoters, expression will be assessed at the transcriptional, translational and metabolic level to produce psymberin intermediates and ultimately the authentic natural product. This work is expected to provide fundamental insights into how renewable sources for complex metabolites can be created that are assembled by poorly studied biosynthetic enzymes of unusual organisms.

越来越多的证据表明，许多从海绵中分离出来的生物活性天然产物是由尚未培养的细菌共生体合成的。然而，迄今为止，这些微生物难以捉摸的生活方式阻碍了对其化学和药理潜力的系统探索。我们小组最近开发了一套宏基因组技术，通过提供生物合成基因的途径，首次证明了海绵衍生聚酮化合物的细菌起源。本研究的目标是开发共生体基因的细菌表达系统，以产生稀有海洋天然产物的可持续生产源。这些研究的模型化合物将是Psymberin，一种从海绵Psammocinia aff分离的实体瘤的有效抑制剂。球根使用各种预先选择的宿主菌株、基因转移系统和启动子，在转录、翻译和代谢水平上评估表达以产生Psymberin中间体并最终产生真正的天然产物。这项工作预计将提供基本的见解，如何可再生资源的复杂代谢物可以创建组装研究不足的生物合成酶的不寻常的生物。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Metabolic and evolutionary origin of actin-binding polyketides from diverse organisms.

DOI：
10.1038/nchembio.1870
发表时间：
2015-09
期刊：
Nature chemical biology
影响因子：
14.8
作者：
Ueoka R;Uria AR;Reiter S;Mori T;Karbaum P;Peters EE;Helfrich EJ;Morinaka BI;Gugger M;Takeyama H;Matsunaga S;Piel J
通讯作者：
Piel J

An environmental bacterial taxon with a large and distinct metabolic repertoire