Planctomycetes as a source of novel secondary metabolites: triggers and regulation of their biosynthesis and engineered production in native strains or heterologous hosts

植物真菌是一门重要的环境细菌，通常与大型和微型藻类等光养生物有关，因此在全球碳氮循环中起着关键作用。几种侧生真菌生长缓慢，倍增时间长达一个月。大多数占据相同生态位的其他异养生物的分裂速度要快得多，但未能胜过Planctomyces。据推测，海洋环境中植物真菌的高丰度是次生代谢物合成的结果，次生代谢物可能是有效的抗菌剂或杀藻剂。植物真菌的复杂生命周期和原核生物相当大的基因组进一步支持了这一观点，这些特征是细菌的典型特征，以其生物活性潜力而闻名。拟议的项目旨在详细描述菌丝菌种的次生代谢组。除了确定新的植物真菌次生代谢物外，还将更详细地分析潜在的生物合成途径及其生产的调节(例如，对环境触发物的反应)。有趣的次生代谢物的生物合成途径随后将通过在可遗传操作的微生物宿主生物(包括已经遗传上可获得的Planctomycates)中的Planctomyctal基因的功能表达来重建。这一战略可以提供对推定影响进行详细分析所需的数量的个别化合物。

Planctomycetes represent a phylum of environmentally important bacteria often associated with phototrophs such as macro- and microalgae and thus play a key role in global carbon and nitrogen cycles. Several planctomycetal species grow slowly with doubling times of up to one month. Most other heterotrophs occupying same ecological niches divide much faster but fail to outcompete Planctomycetes. It is assumed that the high abundance of Planctomycetes in marine environments results from the synthesis of secondary metabolites, which might act as potent antimicrobials or algicidals. This notion is further supported by the complex life cycle of Planctomycetes and quite large genomes for prokaryotes, characteristics that are typical of bacteria known for their bioactive potential. The proposed project aims at a detailed characterization of the secondary metabolome of planctomycetal species. Beyond the identification of novel planctomycetal secondary metabolites, in particular the underlying biosynthetic pathways and the regulation of their production (e.g. as response to environmental triggers) will be analyzed in more detail. Biosynthetic pathways for interesting secondary metabolites will subsequently be reconstructed by functional expression of planctomycetal genes in genetically manipulable microbial host organisms (including already genetically accessible Planctomycetes). This strategy can provide access to individual compounds in amounts required for a detailed analysis of presumed effects.