恶臭假单胞菌潜在次生代谢物和药物样天然产物的全物种基因组挖掘

Sara Aiman, Muhammad Shehroz, Mehwish Munir, Sahib Gul, M. Shah, Asifullah Khan
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引用次数: 12

摘要

恶臭假单胞菌(P.putida)的革兰氏阴性菌对多种生物合成途径的异源表达和大量次级代谢产物的生物合成具有重要意义。编码这种次级代谢产物生物合成蛋白的基因在微生物基因组中被组织成簇,以实现整个生物合成机制的协同表达。公共DNA序列数据库中可获得的50多个不同菌株的完整和全基因组序列为研究生态多样性恶臭假单胞菌菌株的遗传编码次级代谢产物潜力提供了极好的机会。我们利用先进的生物信息学资源对迄今为止可用的P.putida菌株基因组进行注释,用于生物合成基因簇(BGCs),并作为次级代谢产物化学支架的基础。发现P.puida菌株具有基因组特征,编码不同次级代谢产物生物合成的分子机制。这些代谢产物的相应BGC被发现在不同的P.putida菌株中独特分布,推测它们在菌株获得生态能力方面的作用。化学信息学去复制和DrugBank数据库搜索揭示了一种具有2,3,二羟基苯甲酰丝氨酸的假定代谢产物的化学模拟,该代谢产物在先天免疫反应过程中与人类中性粒细胞脂质运载蛋白一起介导抗生素铁耗竭。
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Species-Wide Genome Mining of Pseudomonas putida for Potential Secondary Metabolites and Drug-Like Natural Products Characterization
The gram negative bacteria species of Pseudomonas putida (P. putida) are important for heterologous expression of diverse biosynthetic pathways and numerous secondary metabolites biosynthesis. The genes code for such secondary metabolites biosynthetic proteins are organized in microbial genomes as clusters to bring the concerted expression of entire biosynthetic machinery. The complete and whole genome sequences of more than fifty different strains available in public DNA sequences databases provide an excellent opportunity to investigate the genetically encoded secondary metabolites potential of ecologically diverse P. putida strains. We implement the advance bioinformatics resources to annotate the so far available P. putida strains genomes for biosynthetic gene clusters (BGCs) and underlie secondary metabolites chemical scaffolds. The P. puida strains are found to harbor genomic signatures coding the molecular machinery for diverse secondary metabolites biosynthesis. The corresponding BGCs of these metabolites are found to be uniquely distributed across different P. putida strains speculate their role toward strain's ecological competency acquirement. The chemoinformatics dereplication and DrugBank database searching revealed the chemical mimicry of one putative metabolite with 2, 3, Dihydroxybenzoylserine, that mediates an antibiotic iron depletion along with human neutrophil lipocalin during innate immune response.
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