LetR is a TetR family transcription factor from Lysobacter controlling antifungal antibiotic biosynthesis
LetR is a TetR family transcription factor from Lysobacter controlling antifungal antibiotic biosynthesis
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LetR 是来自 Lysobacter 的 TetR 家族转录因子，控制抗真菌抗生素生物合成
DOI：
10.1007/s00253-017-8117-8
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发表时间：
2017-04-01
影响因子：
5
通讯作者：
Liu, Fengquan
中科院分区：
文献类型：
--
作者：
Wang, Ping;Chen, Hongfu;Liu, Fengquan
热稳定抗真菌因子（HSAF）是一种新发现的广谱抗真菌抗生素，来源于产酶溶杆菌（Lysobacter enzymogenes）。然而，HSAF生物合成的调控机制在L。酶基因仍然知之甚少。在此，我们报告了一个TetR家族蛋白Le1552（LetR）的鉴定。酶基因菌株OH11参与HSAF产生的转录抑制。细菌单杂交和凝胶迁移率变动分析表明，LetR直接结合PHSAF（HSAF生物合成操纵子的启动子区域）。DNA截短测定进一步揭示了PHSAF中负责LetR结合的核心区域。发现野生型OH11中letR的框内缺失显著增加HSAF水平和关键生物合成基因转录，而野生型背景中letR的过表达反而显著降低HSAF水平以及相关基因表达。我们不仅鉴定了一种新的HSAF生物合成调控因子，而且构建了一株高产HSAF的L.酶基因，其在促进用于药物和生物防治目的的HSAF生产方面具有重要价值。
Heat-stable antifungal factor (HSAF) is a newly identified and broad-spectrum antifungal antibiotic from Lysobacter enzymogenes, a ubiquitous environmental proteobacterium. Yet, the regulatory mechanism for HSAF biosynthesis in L. enzymogenes remains poorly understood. Here, we report the identification of a TetR-family protein Le1552 (LetR) from L. enzymogenes strain OH11 that is involved in transcriptional repression of HSAF production. Bacterial one-hybrid and gel mobility shift assays show that LetR directly binds to PHSAF (the promoter region of the HSAF biosynthesis operon). A DNA truncation assay further reveals a core region in PHSAF that is responsible for LetR binding. In-frame deletion of letR in wild-type OH11 is found to significantly increase HSAF levels and key biosynthetic gene transcription, while overexpression of letR in the wild-type background remarkably reduces HSAF levels as well as related gene expression instead. Together, we have identified not only a new regulator for the HSAF biosynthesis but also constructed a higher HSAF-producing deletion strain (ΔletR) of L. enzymogenes, which shall be of great value in promoting HSAF production for pharmaceutical and biological control purposes.