Extracellular signalling, translational control, two repressors and an activator all contribute to the regulation of methylenomycin production in Streptomyces coelicolor
Extracellular signalling, translational control, two repressors and an activator all contribute to the regulation of methylenomycin production in Streptomyces coelicolor
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DOI：
10.1111/j.1365-2958.2008.06560.x
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发表时间：
2009-02-01
影响因子：
3.6
通讯作者：
Chater, Keith F.
中科院分区：
文献类型：
--
作者：
O'Rourke, Sean;Wietzorrek, Andreas;Chater, Keith F.
对与亚甲霉素(MM)生物合成相关的质粒连锁基因簇的生物信息学分析表明，该簇的一部分指导了γ-丁内酯类自动调节因子的合成。自体调节活性可以从培养液中提取，但与γ-丁内酯不同的是耐碱性。该活性最近被证明由一系列新型的自身调节分子--亚甲基霉素呋喃类化合物(简称MMF)组成。MMF自动调节活性被证明解释了某些不产生Mm的突变体在与其他‘转化器’突变体协同合成时充当‘分泌物’的能力。与MMF生物合成有关的三个基因两侧有两个调控基因，这两个基因与γ-丁内酯结合蛋白基因有关。遗传证据表明，这两个基因编码了MMF和MM生物合成的异源寡聚阻滞物的组成部分。MM生物合成基因本身依赖于激活基因mmyB，它似乎被假定的MmyR/MmfR复合体抑制，直到MMF积累足够多的MMF来释放抑制。MmyB和主要的MMF生物合成基因中TTA密码子的存在导致MM的产生依赖于多向性作用的bldA基因，该基因编码很少使用的UUA密码子的tRNA。
Bioinformatic analysis of the plasmid-linked gene cluster associated with biosynthesis of methylenomycin (Mm) suggested that part of the cluster directs synthesis of a gamma-butyrolactone-like autoregulator. Autoregulator activity could be extracted from culture fluids, but differed from gamma-butyrolactones in being alkali resistant. The activity has recently been shown to comprise a series of novel autoregulator molecules, the methylenomycin furans (termed MMF). MMF autoregulator activity is shown to account for the ability of certain Mm non-producing mutants to act as `secretors' in cosynthesis with other `convertor' mutants. Three genes implicated in MMF biosynthesis are flanked by two regulatory genes, which are related to genes for gamma-butyrolactone-binding proteins. Genetic evidence suggests that these two genes encode components of a hetero-oligomeric repressor of MMF and Mm biosynthesis. The Mm biosynthetic genes themselves depend on the activator gene mmyB, which appears to be repressed by the putative MmyR/MmfR complex until enough MMF accumulates to release repression. The presence of TTA codons in mmyB and the main MMF biosynthetic gene causes Mm production to be dependent on the pleiotropically acting bldA gene, which encodes the tRNA for the rarely used UUA codon.