Yue Xin-Jing, Cui Xiao-Wen, Zhang Zheng, Peng Ran, Zhang Peng, Li Zhi-Feng, Li Yue-Zhong
State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, Jinan, 250100, China.
Microb Cell Fact. 2017 May 23;16(1):92. doi: 10.1186/s12934-017-0706-9.
Microbial secondary metabolism is regulated by a complex and mostly-unknown network of global and pathway-specific regulators. A dozen biosynthetic gene clusters for secondary metabolites have been reported in myxobacteria, but a few regulation factors have been identified.
We identified a transcription regulator Esi for the biosynthesis of epothilones. Inactivation of esi promoted the epothilone production, while overexpression of the gene suppressed the production. The regulation was determined to be resulted from the transcriptional changes of epothilone genes. Esi was able to bind, probably via the N-terminus of the protein, to an inverted repeat sequence in the promoter of the epothilone biosynthetic gene cluster. The Esi-homologous sequences retrieved from the RefSeq database are all of the Proteobacteria. However, the Esi regulation is not universal in myxobacteria, because the esi gene exists only in a few myxobacterial genomes.
Esi binds to the epothilone promoter and down-regulates the transcriptional level of the whole gene cluster to affect the biosynthesis of epothilone. This is the first transcription regulator identified for epothilone biosynthesis.
微生物次级代谢受一个复杂且大多未知的全局和途径特异性调控因子网络的调节。在黏细菌中已报道了十几个次级代谢产物的生物合成基因簇，但仅鉴定出了少数调控因子。
我们鉴定出一种用于埃坡霉素生物合成的转录调控因子Esi。Esi失活促进了埃坡霉素的产生，而该基因的过表达则抑制了其产生。这种调控被确定是由埃坡霉素基因的转录变化引起的。Esi可能通过蛋白质的N端与埃坡霉素生物合成基因簇启动子中的反向重复序列结合。从RefSeq数据库中检索到的Esi同源序列均来自变形菌门。然而，Esi调控在黏细菌中并不普遍，因为esi基因仅存在于少数黏细菌基因组中。
Esi与埃坡霉素启动子结合并下调整个基因簇的转录水平，从而影响埃坡霉素的生物合成。这是首次鉴定出的用于埃坡霉素生物合成的转录调控因子。
