Misaki Yuya, Yamamoto Shouji, Suzuki Toshihiro, Iwakuni Miyuki, Sasaki Hiroaki, Takahashi Yuzuru, Inada Kuninobu, Kinashi Haruyasu, Arakawa Kenji
Unit of Biotechnology, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan.
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
Front Microbiol. 2020 Jun 9;11:1089. doi: 10.3389/fmicb.2020.01089. eCollection 2020.
7434AN4, a producer of lankacidin (LC) and lankamycin (LM), carries many regulatory genes including a biosynthesis gene for signaling molecules SRBs (), an SRB receptor gene (), and a SARP ( antibiotic regulatory protein) family activator gene (). Our previous study revealed that the main regulatory cascade goes from through to , leading to LC production, whereas further regulates a second SARP gene to synthesize LM. In this study we extensively investigated the function of , a pseudo-receptor gene, by analyzing antibiotic production and transcription. Metabolite analysis showed that the mutation increased both LC and LM production over four-folds. Transcription, gel shift, and DNase I footprinting experiments revealed that and are expressed under the SRB/SrrA regulatory system, and at the later stage, SrrB represses expression by binding to the promoter region of . These findings confirmed that SrrB acts as a negative regulator of the activator gene to control LC and LM production at the later stage of fermentation in .
7434AN4是兰卡杀菌素（LC）和兰卡霉素（LM）的产生菌，携带许多调控基因，包括信号分子SRBs的生物合成基因（）、SRB受体基因（）和一个SARP（抗生素调控蛋白）家族激活基因（）。我们之前的研究表明，主要的调控级联从 经 到 ，导致LC的产生，而 进一步调控第二个SARP基因 以合成LM。在本研究中，我们通过分析抗生素产生和转录，广泛研究了假受体基因 的功能。代谢物分析表明， 突变使LC和LM的产量均增加了四倍以上。转录、凝胶迁移和DNase I足迹实验表明， 和 在SRB/SrrA调控系统下表达，在后期，SrrB通过结合到 的启动子区域抑制 表达。这些发现证实，SrrB作为激活基因 的负调控因子，在 的发酵后期控制LC和LM的产生。
