Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians
Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians
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DOI：
10.1038/nchembio829
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发表时间：
2006-12-01
影响因子：
14.8
通讯作者：
Schmidt, Eric W.
中科院分区：
文献类型：
--
作者：
Donia, Mohamed S.;Hathaway, Brian J.;Schmidt, Eric W.
一个大家族的细胞毒性环肽的例子patellamides已被分离出海鞘窝藏专性蓝藻共生体Prochloron spp。（1-5）。对这些共生菌的基因组序列分析表明，Prochloron spp.通过核糖体途径合成髌骨酰胺（6）。为了了解这一途径是如何演变为产生一套相关的代谢产物，我们分析了46个含prochloron海鞘从热带太平洋的存在patellamide生物合成基因和分类标记。在这里，我们表明，Prochloron spp。使用保守遗传背景内的小的高变盒产生不同的髌骨酰胺文库。每个共生体菌株都包含一个单一的途径，海鞘内共生体的混合物导致化学文库的积累。我们利用这些信息在大肠杆菌中设计了一种新的环肽的生产，从而证明了对密切相关的共生途径进行比较分析以指导新分子的遗传合成的能力。
A large family of cytotoxic cyclic peptides exemplified by the patellamides has been isolated from ascidians harboring the obligate cyanobacterial symbionts Prochloron spp.(1-5). Genome sequence analysis of these symbionts has revealed that Prochloron spp. synthesize patellamides by a ribosomal pathway(6). To understand how this pathway evolved to produce a suite of related metabolites, we analyzed 46 prochloron-containing ascidians from the tropical Pacific Ocean for the presence of patellamide biosynthetic genes and taxonomic markers. Here, we show that Prochloron spp. generate a diverse library of patellamides using small, hypervariable cassettes within a conserved genetic background. Each symbiont strain contains a single pathway, and mixtures of symbionts within ascidians lead to the accumulation of chemical libraries. We used this information to engineer the production of a new cyclic peptide in Escherichia coli, thereby demonstrating the power of comparative analysis of closely related symbiotic pathways to direct the genetic synthesis of new molecules.