Department of Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.
Department of Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany.
Cell Chem Biol. 2017 May 18;24(5):598-604.e10. doi: 10.1016/j.chembiol.2017.03.017. Epub 2017 Apr 20.
Shewanella algae B516 produces avaroferrin, an asymmetric hydroxamate siderophore, which has been shown to inhibit swarming motility of Vibrio alginolyticus. We aimed to elucidate the biosynthesis of this siderophore and to investigate how S. algae coordinates the production of avaroferrin and its two symmetric counterparts. We reconstituted the reaction in vitro with the main enzyme AvbD and the putative biosynthetic precursors, and demonstrate that multispecificity of this enzyme results in the production of all three cyclic hydroxamate siderophores that were previously isolated as natural products from S. algae. Surprisingly, purified AvbD exhibited a clear preference for the larger cadaverine-derived substrate. In live cells, however, siderophore ratios are maximized toward avaroferrin production, and we demonstrate that these siderophore ratios are the result of a regulation on substrate pool level, which may allow rapid evolutionary adaptation to environmental changes. Our results thereby give insights into a unique evolutionary strategy toward metabolite diversity.
希瓦氏菌 B516 产生阿伐罗啡啉，一种非对称羟肟酸类铁载体，已被证明可抑制 Alg 溶藻弧菌的群集运动。我们旨在阐明这种铁载体的生物合成，并研究希瓦氏菌如何协调阿伐罗啡啉及其两个对称类似物的产生。我们用主要酶 AvbD 和假定的生物合成前体在体外重新构建了反应，并证明该酶的多特异性导致产生了先前从希瓦氏菌中作为天然产物分离出的所有三种环状羟肟酸类铁载体。令人惊讶的是，纯化的 AvbD 对更大的尸胺衍生底物表现出明显的偏好。然而，在活细胞中，铁载体的比例最大程度地朝向阿伐罗啡啉的产生，我们证明这些铁载体的比例是底物池水平调节的结果，这可能允许对环境变化进行快速的进化适应。因此，我们的研究结果深入了解了代谢多样性的独特进化策略。
