Siderophores are small molecule metal chelators secreted in sparse quantities by their native microbial hosts but can be engineered for enhanced production from heterologous hosts like Escherichia coli. These molecules have been proved to be capable of binding heavy metals of commercial and/or environmental interest. In this work, we incorporated, as needed, the appropriate pathways required to produce several siderophores (anguibactin, vibriobactin, bacillibactin, pyoverdine, and enterobactin) into the base E. coli K-12 MG1655 metabolic network model to computationally predict, via flux balance analysis methodologies, gene knockout targets, gene over-expression targets, and media modifications capable of improving siderophore reaction flux. E. coli metabolism proved supportive for the underlying production mechanisms of various siderophores. Within such a framework, the gene deletion and over-expression targets identified, coupled with complementary insights from medium optimization predictions, portend experimental implementation to both enable and improve heterologous siderophore production. Successful production of siderophores would then spur novel metal-binding applications.

铁载体是其天然微生物宿主稀疏分泌的小分子金属螯合剂，但可以进行工程改造以提高大肠杆菌等异源宿主的产量。已经证明这些分子能够结合具有商业和/或环境意义的重金属。在这项工作中，我们根据需要将产生几种铁载体（金葡菌素，弧菌杆菌素，杆菌素，pyoverdine和Enterobactin）所需的适当途径纳入基本大肠杆菌K-12 MG1655代谢网络模型中，以通过通量平衡计算预测分析方法，基因敲除靶标，基因过表达靶标和能够改善铁载体反应通量的培养基修饰。大肠杆菌代谢被证明支持各种铁载体的潜在生产机制。在这样的框架内，确定的基因缺失和过表达靶点，再加上来自培养基优化预测的补充见解，预示着实验的实施，以实现和改善异源铁载体的生产。铁载体的成功生产将刺激新型的金属结合应用。