Identification of butenolide regulatory system controlling secondary metabolism in Streptomyces albus J1074.

Identification of butenolide regulatory system controlling secondary metabolism in Streptomyces albus J1074.
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鉴定丁烯乙烯酯调节系统控制了Albus J1074链霉菌中的继发代谢。

DOI:
10.1038/s41598-017-10316-y
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发表时间:
2017-08-29
期刊:
影响因子:
4.6
通讯作者:
Luzhetskyy A
Luzhetskyy A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ahmed Y;Rebets Y;Tokovenko B;Brötz E;Luzhetskyy A

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放线菌基因组加密的化学多样性中有很大一部分尚未被发现,这与次级代谢基因表达水平低有关。在这里,我们报告的应用程序的细菌引导的筛选策略,以激活隐藏的多环tetramate大环内酰胺基因簇在白色链霉菌J1074。对S.转录组显示,白对虾次级代谢基因转录水平总体较低。结合转座子诱变,筛选出两株S。具有改变的次级代谢产物产生的白色菌株。转座子插入最突出的菌株,S。albus ATGSal2P2::TN14定位于编码未分类转录调节因子的XNR_3174基因。发现该突变株产生类似燕麦内酯的化合物丁烯酰草胺4。缺失的基因编码一个假定的酰基辅酶A氧化酶,直向同源的链霉菌avermiastrium avenescens生物合成酶,在S。albus XNR_3174突变体引起次生代谢沉默。XNR_3174和丁烯酰亚胺生物合成基因的同源物在多个链霉菌属物种的基因组中被发现。这一结果使我们相信,所发现的调控元件包括一个新的条件依赖性系统,控制放线菌中的次生代谢,并可以被操纵来激活隐蔽的生物合成途径。
A large majority of genome-encrypted chemical diversity in actinobacteria remains to be discovered, which is related to the low level of secondary metabolism genes expression. Here, we report the application of a reporter-guided screening strategy to activate cryptic polycyclic tetramate macrolactam gene clusters in Streptomyces albus J1074. The analysis of the S. albus transcriptome revealed an overall low level of secondary metabolism genes transcription. Combined with transposon mutagenesis, reporter-guided screening resulted in the selection of two S. albus strains with altered secondary metabolites production. Transposon insertion in the most prominent strain, S. albus ATGSal2P2::TN14, was mapped to the XNR_3174 gene encoding an unclassified transcriptional regulator. The mutant strain was found to produce the avenolide-like compound butenolide 4. The deletion of the gene encoding a putative acyl-CoA oxidase, an orthologue of the Streptomyces avermitilis avenolide biosynthesis enzyme, in the S. albus XNR_3174 mutant caused silencing of secondary metabolism. The homologues of XNR_3174 and the butenolide biosynthesis genes were found in the genomes of multiple Streptomyces species. This result leads us to believe that the discovered regulatory elements comprise a new condition-dependent system that controls secondary metabolism in actinobacteria and can be manipulated to activate cryptic biosynthetic pathways.
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