Clostridium saccharoperbutylacetonicum N1-4 (Csa) is a historically significant anaerobic bacterium which can perform saccharolytic fermentations to produce acetone, butanol, and ethanol (ABE). Recent genomic analyses have highlighted this organism's potential to produce polyketide and nonribosomal peptide secondary metabolites, but little is known regarding the identity and function of these metabolites. This study provides a detailed bioinformatic analysis of seven biosynthetic gene clusters (BGCs) present in the Csa genome that are predicted to produce polyketides/nonribosomal peptides. An RNA-seq-based untargeted transcriptomic approach revealed that five of seven BGCs were expressed during ABE fermentation. Additional characterization of a highly expressed nonribosomal peptide synthetase gene led to the discovery of its associated metabolite and its biosynthetic pathway. Transcriptomic analysis suggested an association of this nonribosomal peptide synthetase gene with butanol tolerance, which was supported by butanol challenge assays.

中文翻译：

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工业丁醇高产梭状芽孢杆菌N1-4梭菌的次级代谢研究。

蔗糖丁基丙酮梭菌N1-4（Csa）是一种具有历史意义的厌氧细菌，可进行糖酵解发酵以生产丙酮，丁醇和乙醇（ABE）。最近的基因组分析突出了该生物体产生聚酮化合物和非核糖体肽二级代谢产物的潜力，但对于这些代谢产物的特性和功能知之甚少。这项研究提供了对Csa基因组中存在的七个生物合成基因簇（BGC）的详细生物信息学分析，这些簇预计会产生聚酮化合物/非核糖体肽。基于RNA序列的非靶向转录组方法显示，在ABE发酵过程中表达了七个BGC中的五个。高表达的非核糖体肽合成酶基因的其他特征导致其相关代谢产物及其生物合成途径的发现。转录组学分析表明该非核糖体肽合成酶基因与丁醇耐受性相关，这在丁醇攻击试验中得到了支持。