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乙酰转移酶SCO0988正向调控模式菌株和中的特殊代谢及形态分化。

The acetyltransferase SCO0988 controls positively specialized metabolism and morphological differentiation in the model strains and .

作者信息

Bi Yunwen, An Hao, Chi Zhewei, Xu Zhongheng, Deng Yuan, Ren Yuxian, Wang Rui, Lu Xinyi, Guo Jia, Hu Ren, Virolle Marie-Joelle, Xu Delin

机构信息

Department of Ecology, Institute of Hydrobiology, School of Life Science and Technology, Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, Engineering Research Center of Tropical and Subtropical Aquatic Ecological Engineering, Ministry of Education, Jinan University, Guangzhou, China.

Université Paris-Saclay, CNRS, CEA, Institute for Integrative Biology of the Cell (I2BC), Department of Microbiology, Group "Energetic Metabolism of Streptomyces", Gif-sur-Yvette, France.

出版信息

Front Microbiol. 2024 Jul 24;15:1366336. doi: 10.3389/fmicb.2024.1366336. eCollection 2024.

Abstract

Streptomycetes are well-known antibiotic producers possessing in their genomes numerous silent biosynthetic pathways that might direct the biosynthesis of novel bio-active specialized metabolites. It is thus of great interest to find ways to enhance the expression of these pathways to discover most needed novel antibiotics. In this study, we demonstrated that the over-expression of acetyltransferase SCO0988 up-regulated the production of specialized metabolites and accelerated sporulation of the weak antibiotic producer, and that the deletion of this gene had opposite effects in the strong antibiotic producer, . The comparative analysis of the acetylome of a strain over-expressing with that of the original strain revealed that SCO0988 acetylates a broad range of proteins of various pathways including BldKB/SCO5113, the extracellular solute-binding protein of an ABC-transporter involved in the up-take of a signal oligopeptide of the quorum sensing pathway. The up-take of this oligopeptide triggers the "bald cascade" that regulates positively specialized metabolism, aerial mycelium formation and sporulation in . Interestingly, BldKB/SCO5113 was over-acetylated on four Lysine residues, including Lys, upon SCO0988 over-expression. The bald phenotype of a mutant could be complemented by native but not by variant of in which the Lys was replaced by arginine, an amino acid that could not be acetylated or by glutamine, an amino acid that is expected to mimic acetylated lysine. Our study demonstrated that Lys was a critical residue for BldKB function but was inconclusive concerning the impact of acetylation of Lys on BldKB function.

摘要

链霉菌是著名的抗生素产生菌,其基因组中拥有众多沉默的生物合成途径,这些途径可能指导新型生物活性特殊代谢产物的生物合成。因此,找到增强这些途径表达以发现最急需的新型抗生素的方法具有极大的意义。在本研究中,我们证明乙酰转移酶SCO0988的过表达上调了特殊代谢产物的产量,并加速了弱抗生素产生菌的孢子形成,而在强抗生素产生菌中删除该基因则产生相反的效果。对过表达该基因的菌株与原始菌株的乙酰化蛋白质组进行比较分析发现,SCO0988使包括BldKB/SCO5113在内的各种途径的多种蛋白质乙酰化,BldKB/SCO5113是一种ABC转运蛋白的细胞外溶质结合蛋白,参与群体感应途径信号寡肽的摄取。这种寡肽的摄取触发“光秃级联反应”,正向调节链霉菌中的特殊代谢、气生菌丝形成和孢子形成。有趣的是,在SCO0988过表达时,BldKB/SCO5113在四个赖氨酸残基上过度乙酰化,包括赖氨酸。链霉菌突变体的光秃表型可以被天然的链霉菌补充,但不能被赖氨酸被精氨酸(一种不能被乙酰化的氨基酸)或谷氨酰胺(一种预期可模拟乙酰化赖氨酸的氨基酸)取代的变体补充。我们的研究表明赖氨酸是BldKB功能的关键残基,但关于赖氨酸乙酰化对BldKB功能的影响尚无定论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e55/11303876/ec61719094c5/fmicb-15-1366336-g004.jpg

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