Institute of Biochemistry and Biology, University of Potsdam, Karl-Liebknecht-Str. 24/25, 14476, Potsdam-Golm, Germany.
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstr. 11a, 07745, Jena, Germany.
Angew Chem Int Ed Engl. 2022 Jun 27;61(26):e202204545. doi: 10.1002/anie.202204545. Epub 2022 May 9.
Genomes of cyanobacteria feature a variety of cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting the discovery and exploitation of the metabolic dark matter are not well understood. Here we describe the discovery of two cell density-dependent chemical mediators, nostoclide and nostovalerolactone, in the symbiotic model strain Nostoc punctiforme, and demonstrate their pronounced impact on the regulation of specialized metabolism. Through transcriptional, bioinformatic and labeling studies we assigned two adjacent biosynthetic gene clusters to the biosynthesis of the two polyketide mediators. Our findings provide insight into the orchestration of specialized metabolite production and give lessons for the genomic mining and high-titer production of cyanobacterial bioactive compounds.
蓝藻基因组具有多种用于复杂天然产物的隐匿生物合成途径，但限制代谢暗物质发现和利用的特殊性尚不清楚。在这里，我们描述了共生模型菌株念珠藻中两种细胞密度依赖性化学介体 Nostoclide 和 Nostovalerolactone 的发现，并证明了它们对特殊代谢物调控的显著影响。通过转录组学、生物信息学和标记研究，我们将两个相邻的生物合成基因簇分配到两种聚酮介导物的生物合成中。我们的发现深入了解了特殊代谢产物产生的协调作用，并为蓝藻生物活性化合物的基因组挖掘和高产提供了经验。
