Liu Zhixiang, Huang Tingting, Shi Qing, Deng Zixin, Lin Shuangjun
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory on Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Haihe Laboratory of Synthetic Biology, Tianjin, China.
Front Microbiol. 2023 May 3;14:1182449. doi: 10.3389/fmicb.2023.1182449. eCollection 2023.
Enterobactin is an archetypical catecholate siderophore that plays a key role in the acquisition of ferric iron by microorganisms. Catechol moieties have been shown to be promising siderophore cores. Variants of the conserved 2,3-dihydroxybenzoate (DHB) moiety with structural modifications expand the bioactivity. are characterized by metabolites with diverse structures. The genomic sequence of indicated that it possessed a biosynthetic gene cluster for DHB containing siderophores and metabolic profiling revealed metabolites correlated with catechol-type natural products. Here, we report the discovery of a series of catecholate siderophores produced by and a scale-up fermentation was performed to purify these compounds for structural elucidation. A biosynthetic route for the catecholate siderophores is also proposed. These new structural features enrich the structural diversity of the enterobactin family compounds. One of the new linear enterobactin congeners shows moderate activity against a food-borne pathogen . This work demonstrated that changing culture conditions is still a promising approach to explore unexplored chemical diversity. The availability of the biosynthetic machinery will enrich the genetic toolbox of catechol siderophores and facilitate such engineering efforts.
肠杆菌素是一种典型的儿茶酚型铁载体，在微生物获取三价铁的过程中发挥关键作用。儿茶酚部分已被证明是很有前景的铁载体核心。具有结构修饰的保守2,3 - 二羟基苯甲酸（DHB）部分的变体扩展了生物活性。其特点是代谢产物具有多样的结构。[具体微生物名称]的基因组序列表明它拥有一个用于含DHB的铁载体的生物合成基因簇，代谢谱分析揭示了与儿茶酚型天然产物相关的代谢产物。在此，我们报告了[具体微生物名称]产生的一系列儿茶酚型铁载体的发现，并进行了放大发酵以纯化这些化合物用于结构解析。还提出了儿茶酚型铁载体的生物合成途径。这些新的结构特征丰富了肠杆菌素家族化合物的结构多样性。其中一种新的线性肠杆菌素同系物对一种食源性病原体显示出中等活性。这项工作表明改变培养条件仍然是探索未开发化学多样性的一种有前景的方法。生物合成机制的可用性将丰富儿茶酚铁载体的基因工具库并促进此类工程努力。
