Center for Systems Microbiology, Department of Systems Biology, Technical University of Denmark, Building 301, DK-2800 Lyngby, Denmark.
Appl Environ Microbiol. 2009 Nov;75(21):6688-95. doi: 10.1128/AEM.00943-09. Epub 2009 Sep 11.
Nisin is a natural bacteriocin produced commercially by Lactococcus lactis and widely used in the food industry as a preservative because of its broad host spectrum. Despite the low productivity and troublesome fermentation of L. lactis, no alternative cost-effective host has yet been found. Bacillus subtilis had been suggested as a potential host for the biosynthesis of nisin but was discarded due to its sensitivity to the lethal action of nisin. In this study, we have reevaluated the potential of B. subtilis as a host organism for the heterologous production of nisin. We applied transcriptome and proteome analyses of B. subtilis and identified eight genes upregulated in the presence of nisin. We demonstrated that the overexpression of some of these genes boosts the natural defenses of B. subtilis, which allows it to sustain higher levels of nisin in the medium. We also attempted to overcome the nisin sensitivity of B. subtilis by introducing the nisin resistance genes nisFEG and nisI from L. lactis under the control of a synthetic promoter library.
乳链菌肽是一种由乳酸乳球菌商业化生产的天然细菌素，由于其广谱宿主谱，被广泛应用于食品工业作为防腐剂。尽管乳酸乳球菌的生产力低，发酵过程麻烦，但尚未找到具有成本效益的替代宿主。枯草芽孢杆菌曾被提议作为合成乳链菌肽的潜在宿主，但由于其对乳链菌肽的致命作用敏感而被摒弃。在这项研究中，我们重新评估了枯草芽孢杆菌作为异源生产乳链菌肽的宿主的潜力。我们应用了枯草芽孢杆菌的转录组和蛋白质组分析，并鉴定出了 8 个在乳链菌肽存在下上调的基因。我们证明，这些基因中的一些过表达可以增强枯草芽孢杆菌的天然防御能力，使其能够在培养基中维持更高水平的乳链菌肽。我们还试图通过在合成启动子文库的控制下，从乳酸乳球菌引入乳链菌肽抗性基因 nisFEG 和 nisI，来克服枯草芽孢杆菌对乳链菌肽的敏感性。
