High-Density Cultivation of Terrestrial Nostoc Strains Leads to Reprogramming of Secondary Metabolome
High-Density Cultivation of Terrestrial Nostoc Strains Leads to Reprogramming of Secondary Metabolome
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DOI：
10.1128/aem.01510-17
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发表时间：
2017-12-01
影响因子：
4.4
通讯作者：
Dittmann, Elke
中科院分区：
文献类型：
--
作者：
Guljamow, Arthur;Kreische, Marco;Dittmann, Elke
陆生共生蓝藻属念珠藻表现出很大的潜力，生产的生物活性的天然产物的非核糖体肽，聚酮化合物，和核糖体肽类，但大多数的生物合成基因簇是沉默的，在传统的培养条件下。在本研究中，我们利用了一种高密度培养方法，最近开发的光合细菌迅速产生的丝状细菌的生物量高达400克（湿重）/升的密度。出乎意料的是，整合的转录和代谢组学研究发现了一个主要的二次代谢组的念珠藻菌株在高培养密度和在这个过程中的胞外信号的支配作用重编程。整体的方法，使捕捉和结构阐明的鱼腥藻肽素的新的变体，包括一个同源物与强大的化感活性对菌株分离自相同的栖息地。这项研究提供了一个快照上的作用，细胞类型特异性表达的天然产物的形成在cyanobacteri.IMPORTANCE陆地丝状蓝藻是一个很大程度上未开发的小分子天然产物的来源。光养生物的开发受到其缓慢生长和光生物反应器需求的阻碍。本研究不仅证明了最近开发的双层容器培养方法的适用性，用于快速生成念珠藻菌株的生物量，而且还证明了高价值的天然产物在高培养密度下的显著上调。该研究为高通量筛选和开发小分子天然产物提供了新的指导，并有助于发现陆地蓝藻中新的生物活性产物。
Terrestrial symbiotic cyanobacteria of the genus Nostoc exhibit a large potential for the production of bioactive natural products of the nonribosomal peptide, polyketide, and ribosomal peptide classes, and yet most of the biosynthetic gene clusters are silent under conventional cultivation conditions. In the present study, we utilized a high-density cultivation approach recently developed for phototrophic bacteria to rapidly generate biomass of the filamentous bacteria up to a density of 400 g (wet weight)/liter. Unexpectedly, integrated transcriptional and metabolomics studies uncovered a major reprogramming of the secondary metabolome of two Nostoc strains at high culture density and a governing effect of extracellular signals in this process. The holistic approach enabled capturing and structural elucidation of novel variants of anabaenopeptin, including one congener with potent allelopathic activity against a strain isolated from the same habitat. The study provides a snapshot on the role of cell-type-specific expression for the formation of natural products in cyanobacteria.IMPORTANCE Terrestrial filamentous cyanobacteria are a largely untapped source of small-molecule natural products. Exploitation of the phototrophic organisms is hampered by their slow growth and the requirement of photobioreactors. The present study not only demonstrates the suitability of a recently developed two-tier vessel cultivation approach for the rapid generation of biomass of Nostoc strains but also demonstrates a pronounced upregulation of high value natural products at ultrahigh culture densities. The study provides new guidelines for high-throughput screening and exploitation of small-molecule natural products and can facilitate the discovery new bioactive products from terrestrial cyanobacteria.