State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, People's Republic of China.
Appl Environ Microbiol. 2011 Jan;77(2):407-15. doi: 10.1128/AEM.01278-10. Epub 2010 Nov 12.
Streptococcus bovis HJ50 produces a lacticin 481-like 33-amino-acid-residue lantibiotic, designated bovicin HJ50. bovK-bovR in the bovicin HJ50 biosynthetic gene cluster is predicted to be a two-component signal transduction system involved in sensing signals and regulating gene expression. Disruption of bovK or bovR resulted in the abrogation of bovicin HJ50 production, suggesting both genes play important roles in bovicin HJ50 biosynthesis. Addition of exogenous bovicin HJ50 peptide to cultures of a bovM mutant that lost the capability for bovicin HJ50 production and structural gene bovA transcription in S. bovis HJ50 induced dose-dependent transcription of the bovA gene, demonstrating that bovicin HJ50 production was normally autoregulated. The transcription of bovA was no longer induced by bovicin HJ50 in bovK and bovR disruption mutants, suggesting that BovK-BovR plays an essential role in the signal transduction regulating bovicin HJ50 biosynthesis. A phosphorylation assay indicated that BovK has the ability to autophosphorylate and subsequently transfer the phosphoryl group to the downstream BovR protein to carry on signal transduction. Electromobility shift assays (EMSA) and green fluorescent protein (GFP) reporter gene expression assays showed the specific binding of BovR to the bovA promoter, indicating that BovR regulates bovA expression by direct binding between them. Taken together, bovicin HJ50 biosynthesis is induced by bovicin HJ50 itself and regulated via the two-component signal transduction system BovK-BovR.
猪链球菌 HJ50 产生一种类似于乳链菌肽 481 的 33 个氨基酸残基的类细菌素，命名为 bovicin HJ50。bovicin HJ50 生物合成基因簇中的 bovK-bovR 被预测为一个涉及感应信号和调节基因表达的双组分信号转导系统。bovK 或 bovR 的缺失导致 bovicin HJ50 生产的中断，这表明这两个基因在 bovicin HJ50 生物合成中都发挥着重要作用。将外源性 bovicin HJ50 肽添加到失去生产 bovicin HJ50 和结构基因 bovA 转录能力的 S. bovis HJ50 中的 bovM 突变体的培养物中，诱导 bovA 基因的剂量依赖性转录，表明 bovicin HJ50 的生产是正常的自调控的。在 bovK 和 bovR 缺失突变体中，bovicin HJ50 不再诱导 bovA 的转录，这表明 BovK-BovR 在调节 bovicin HJ50 生物合成的信号转导中发挥着重要作用。磷酸化测定表明 BovK 具有自身磷酸化的能力，并随后将磷酸基团转移到下游的 BovR 蛋白上，以进行信号转导。电泳迁移率变动分析（EMSA）和绿色荧光蛋白（GFP）报告基因表达分析显示 BovR 与 bovA 启动子的特异性结合，表明 BovR 通过它们之间的直接结合来调节 bovA 的表达。综上所述，bovicin HJ50 的生物合成是由 bovicin HJ50 自身诱导的，并通过双组分信号转导系统 BovK-BovR 进行调节。
