Dinesen Caja, Vertot Manca, Jarmusch Scott A, Lozano-Andrade Carlos N, Andersen Aaron J C, Kovács Ákos T
DTU Bioengineering, Technical University of Denmark, 2800 Kgs Lyngby, Denmark.
Institute of Biology, Leiden University, 2333 BE Leiden, The Netherlands.
Microlife. 2025 Jan 2;6:uqae029. doi: 10.1093/femsml/uqae029. eCollection 2025.
Although not essential for their growth, the production of secondary metabolites increases the fitness of the producing microorganisms in their natural habitat by enhancing establishment, competition, and nutrient acquisition. The Gram-positive soil-dwelling bacterium, , produces a variety of secondary metabolites. Here, we investigated the regulatory relationship between the non-ribosomal peptide surfactin and the sactipeptide bacteriocin subtilosin A. We discovered that mutants lacking surfactin production exhibited higher production of subtilosin A compared to their parental wild-type strain. Additionally, spatial visualization of production of metabolites demonstrated that surfactin secreted by a wild-type colony could suppress subtilosin A production in an adjacent mutant colony lacking surfactin production. Reporter assays were performed using mutants in specific transcriptional regulators, which confirmed the role of ResD as an activator of the subtilosin A encoding biosynthetic gene cluster (BGC), while the removal of Rok and AbrB repressors increased the expression of the BGC, which was further enhanced by additional deletion of surfactin, suggesting that a so-far-unidentified regulator might mediate the influence of surfactin on production of subtilosin A. Our study reveals a regulatory influence of one secondary metabolite on another, highlighting that the function of secondary metabolites could be more complex than its influence on other organisms and interactions among secondary metabolites could also contribute to their ecological significance.
虽然次级代谢产物的产生并非微生物生长所必需，但它通过增强定殖、竞争和养分获取能力，提高了产生这些次级代谢产物的微生物在其自然栖息地中的适应性。革兰氏阳性土壤细菌枯草芽孢杆菌会产生多种次级代谢产物。在此，我们研究了非核糖体肽表面活性素与硫肽类细菌素枯草菌素A之间的调控关系。我们发现，与亲本野生型菌株相比，缺乏表面活性素产生的枯草芽孢杆菌突变体表现出更高的枯草菌素A产量。此外，对代谢产物产生情况的空间可视化显示，野生型菌落分泌的表面活性素能够抑制相邻的缺乏表面活性素产生的突变体菌落中枯草菌素A的产生。我们使用特定转录调节因子的突变体进行了报告基因检测，证实ResD作为枯草菌素A编码生物合成基因簇（BGC）的激活因子发挥作用，而去除Rok和AbrB阻遏物会增加BGC的表达，表面活性素的额外缺失进一步增强了这种表达，这表明可能存在一个尚未鉴定的调节因子介导表面活性素对枯草菌素A产生的影响。我们的研究揭示了一种次级代谢产物对另一种次级代谢产物的调控影响，突出了次级代谢产物的功能可能比其对其他生物体的影响更为复杂，并且次级代谢产物之间的相互作用也可能对它们的生态意义有所贡献。
