Efficient bacterial cell factories are important for the screening and characterization of potent antimicrobial peptides such as lantibiotics. Although lantibiotic production systems have been established in Lactococcus lactis and Escherichia coli, the industrial workhorse Bacillus subtilis has been left relatively unexplored as a lantibiotic production host. Therefore, we tested different B. subtilis strains for their ability to produce lantibiotic peptides by using the subtilin modification and transport enzymes derived from the natural subtilin producer B. subtilis ATCC 6633. Our study shows that although B. subtilis ATCC 6633 and 168 are able to produce various processed lantibiotic peptides, an evident advantage of using either the 8-fold protease-deficient strain WB800 or the genome-minimized B. subtilis 168 strain PG10 is the lack of extracellular serine protease activity. Consequently, leader processing of lantibiotic precursor peptides is circumvented and thus potential toxicity toward the production host is prevented. Furthermore, PG10 provides a clean secondary metabolic background and therefore appears to be the most promising B. subtilis lantibiotic production host. We demonstrate the production of various lantibiotic precursor peptides by PG10 and show different options for their in vitro activation. Our study thus provides a convenient B. subtilis-based lantibiotic production system, which facilitates the search for novel antimicrobial peptides.

中文翻译：

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MiniBacillus PG10作为羊毛硫抗生素的便捷有效生产宿主。

有效的细菌细胞工厂对于有效的抗菌肽（如羊毛硫抗生素）的筛选和表征很重要。尽管在乳酸乳球菌和大肠杆菌中已经建立了羊毛硫抗生素生产系统，但作为羊毛硫抗生素生产宿主，工业上的枯草芽孢杆菌枯草芽孢杆菌尚未得到开发。因此，我们测试了不同的枯草芽孢杆菌菌株通过使用天然枯草杆菌生产者枯草芽孢杆菌ATCC 6633衍生的枯草蛋白酶修饰和转运酶来生产羊毛硫抗生素肽的能力。我们的研究表明，尽管枯草芽孢杆菌ATCC 6633和168能够产生各种加工的羊毛硫抗生素肽，使用8倍蛋白酶缺陷菌株WB800或基因组最小化枯草芽孢杆菌168菌株PG10的明显优势是缺乏细胞外丝氨酸蛋白酶活性。因此，避免了羊毛硫抗生素前体肽的前导处理，从而防止了对生产宿主的潜在毒性。此外，PG10提供了干净的次级代谢背景，因此似乎是最有希望的枯草芽孢杆菌羊毛硫抗生素生产宿主。我们演示了由PG10产生的多种羊毛硫抗生素前体肽，并显示了其体外激活的不同选择。因此我们的研究提供了方便基于枯草芽孢杆菌的羊毛硫抗生素生产系统，它有助于寻找新的抗菌肽。