Bacteriocins are antimicrobial peptides produced by bacteria to inhibit competitors in their natural environments. Some of these peptides have emerged as commercial food preservatives and, due to the rapid increase in antibiotic resistant bacteria, are also discussed as interesting alternatives to antibiotics for therapeutic purposes. Currently, commercial bacteriocins are produced exclusively with natural producer organisms on complex substrates and are sold as semi-purified preparations or crude fermentates. To allow clinical application, efficacy of production and purity of the product need to be improved. This can be achieved by shifting production to recombinant microorganisms.

Here, we identify Corynebacterium glutamicum as a suitable production host for the bacteriocin pediocin PA-1. C. glutamicum CR099 shows resistance to high concentrations of pediocin PA-1 and the bacteriocin was not inactivated when spiked into growing cultures of this bacterium. Recombinant C. glutamicum expressing a synthetic pedACD^Cgl operon releases a compound that has potent antimicrobial activity against Listeria monocytogenes and Listeria innocua and matches size and mass:charge ratio of commercial pediocin PA-1. Fermentations in shake flasks and bioreactors suggest that low levels of dissolved oxygen are favorable for production of pediocin. Under these conditions, however, reduced activity of the TCA cycle resulted in decreased availability of the important pediocin precursor l-asparagine suggesting options for further improvement. Overall, we demonstrate that C. glutamicum is a suitable host for recombinant production of bacteriocins of the pediocin family.

细菌素是细菌产生的抗菌肽，用于抑制自然环境中的竞争者。这些肽中的一些已经作为商业食品防腐剂出现，并且由于抗生素抗性细菌的迅速增加，也被讨论为用于治疗目的的抗生素的有趣替代品。目前，商业细菌素仅由天然生产生物在复杂基质上生产，并作为半纯化制剂或粗发酵物出售。为实现临床应用，需要提高产品的生产效率和纯度。这可以通过将生产转移到重组微生物来实现。

在这里，我们将谷氨酸棒状杆菌确定为细菌素片菌素 PA-1 的合适生产宿主。C. glutamicum CR099 显示出对高浓度 pediocin PA-1 的抗性，并且当掺入这种细菌的生长培养物中时，该细菌素并未失活。表达合成pedACD ^Cgl操纵子的重组谷氨酸棒杆菌释放一种化合物，该化合物对单核细胞增生李斯特菌和无害李斯特菌具有强效抗菌活性并匹配商业片碱 PA-1 的大小和质量：电荷比。摇瓶和生物反应器中的发酵表明低水平的溶解氧有利于产生片碱。然而，在这些条件下，TCA 循环的活性降低导致重要的片碱前体l-天冬酰胺的可用性降低，这表明了进一步改进的选择。总的来说，我们证明谷氨酸棒杆菌是重组生产片菌素家族细菌素的合适宿主。