Shi Haoran, Wang Jiabin, Zhang Xuedong, Zhou Na, Wang Xiangjing, Xiang Wensheng, Li Shanshan, Zhang Yanyan
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, China.
Key Laboratory of Agricultural Microbiology of Heilongjiang Province, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin 150030, China.
Biology (Basel). 2025 Jul 4;14(7):813. doi: 10.3390/biology14070813.
Guvermectin, a -derived purine nucleoside compound, exhibits dual bioactivities as a plant growth regulator and an antibacterial agent. While its biosynthetic gene cluster (BGC) is regulated by the cluster-situated activator GvmR and the adjacent repressor GvmR2, the role of distal transcriptional regulators (TRs) in guvermectin biosynthesis remains unexplored. Here, we identified ScnR1, a highly conserved LacI-family TR located far from the guvermectin BGC, which is directly activated by GvmR. Overexpression of significantly suppressed guvermectin biosynthesis. Further investigations revealed that ScnR1 competitively binds to the , , and promoters (overlapping with the GvmR-binding sites), thereby inhibiting the guvermectin BGC transcription. Moreover, ScnR1 formed a reciprocal feedback loop with the adjacent repressor GvmR2, where each repressor inhibits the other's expression. These findings reveal a multi-layered regulatory mechanism wherein LacI-family TRs fine-tune guvermectin biosynthesis through competitive DNA binding and reciprocal feedback control. This study offers new perspectives on the hierarchical control of secondary metabolism in and provides valuable theoretical guidance for the engineering of strains with enhanced natural product production.
谷韦菌素是一种嘌呤核苷类化合物，具有植物生长调节剂和抗菌剂的双重生物活性。虽然其生物合成基因簇（BGC）受位于簇内的激活剂GvmR和相邻的阻遏物GvmR2调控，但远端转录调节因子（TRs）在谷韦菌素生物合成中的作用仍未得到探索。在此，我们鉴定出ScnR1，一种高度保守的LacI家族TR，其位于远离谷韦菌素BGC的位置，它直接被GvmR激活。ScnR1的过表达显著抑制了谷韦菌素的生物合成。进一步研究表明，ScnR1竞争性结合 、 和 启动子（与GvmR结合位点重叠），从而抑制谷韦菌素BGC的转录。此外，ScnR1与相邻的阻遏物GvmR2形成了一个相互反馈环，其中每个阻遏物抑制另一个的表达。这些发现揭示了一种多层次的调控机制，其中LacI家族TRs通过竞争性DNA结合和相互反馈控制来微调谷韦菌素的生物合成。本研究为 中次级代谢的分层控制提供了新的视角，并为工程改造提高天然产物产量的菌株提供了有价值的理论指导。
