Streptomyces γ-butyrolactones (GBLs) are quorum sensing communication signals triggering antibiotic production. The GBL system of Streptomyces filipinensis, the producer of the antifungal agent filipin, has been investigated. Inactivation of sfbR (for S. filipinensis γ-butyrolactone receptor), a GBL receptor, resulted in a strong decrease in production of filipin, and deletion of sfbR2, a pseudo-receptor, boosted it, in agreement with lower and higher levels of transcription of filipin biosynthetic genes, respectively. It is noteworthy that none of the mutations affected growth or morphological development. While no ARE (autoregulatory element)-like sequences were found in the promoters of filipin genes, suggesting indirect control of production, five ARE sequences were found in five genes of the GBL cluster, whose transcription has been shown to be controlled by both S. filipinensis SfbR and SfbR2. In vitro binding of recombinant SfbR and SfbR2 to such sequences indicated that such control is direct. Transcription start points were identified by 5′ rapid amplification of cDNA ends, and precise binding regions were investigated by the use of DNase I protection studies. Binding of both regulators took place in the promoter of target genes and at the same sites. Information content analysis of protected sequences in target promoters yielded an 18-nucleotide consensus ARE sequence. Quantitative transcriptional analyses revealed that both regulators are self-regulated and that each represses the transcription of the other as well as that of the remaining target genes. Unlike other GBL receptor homologues, SfbR activates its own transcription whereas SfbR2 has a canonical autorepression profile. Additionally, SfbR2 was found here to bind the antifungal antimycin A as a way to modulate its DNA-binding activity.

中文翻译：

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菲律宾链霉菌γ-丁内酯系统揭示了了解次级代谢控制的新型线索。

链霉菌γ-丁内酯（GBL）是群体感应通信信号，可触发抗生素的产生。已研究了抗真菌剂菲利宾的生产者菲律宾链霉菌的GBL系统。的失活SFBR（对于小号。˚F ilipinensis γ- b utyrolactone ř eceptor），一个GBL受体，导致生产菲律宾菌素的强烈降低，缺失sfbR2假受体的增强，使其分别与菲律宾生物合成基因的较低和较高转录水平一致。值得注意的是，没有一个突变影响生长或形态发育。虽然在菲律宾基因的启动子中未发现类似ARE（自动调节元件）的序列，这暗示了对生产的间接控制，但在GBL簇的五个基因中发现了五个ARE序列，已证明其转录受两个S的控制。菲律宾SfbR和SfbR2。体外重组SfbR和SfbR2与此类序列的结合表明这种控制是直接的。通过cDNA末端的5'快速扩增来识别转录起点，并通过使用DNase I保护研究来研究精确的结合区域。两种调节剂的结合均在靶基因的启动子中和相同位点发生。靶启动子中受保护序列的信息含量分析产生了18个核苷酸的共有ARE序列。定量转录分析表明，两个调节子都是自我调节的，并且每个都抑制另一个以及其余靶基因的转录。与其他GBL受体同源物不同，SfbR激活其自身的转录，而SfbR2具有规范的自动抑制特性。另外，