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海洋微生物勘探中新型生物合成基因簇的探索。

Exploring Newer Biosynthetic Gene Clusters in Marine Microbial Prospecting.

机构信息

Centre for Drug Discovery and Development, Sathyabama Institute of Science and Technology, Chennai, 600 119, Tamil Nadu, India.

出版信息

Mar Biotechnol (NY). 2022 Jun;24(3):448-467. doi: 10.1007/s10126-022-10118-y. Epub 2022 Apr 8.

Abstract

Marine microbes genetically evolved to survive varying salinity, temperature, pH, and other stress factors by producing different bioactive metabolites. These microbial secondary metabolites (SMs) are novel, have high potential, and could be used as lead molecule. Genome sequencing of microbes revealed that they have the capability to produce numerous novel bioactive metabolites than observed under standard in vitro culture conditions. Microbial genome has specific regions responsible for SM assembly, termed biosynthetic gene clusters (BGCs), possessing all the necessary genes to encode different enzymes required to generate SM. In order to augment the microbial chemo diversity and to activate these gene clusters, various tools and techniques are developed. Metagenomics with functional gene expression studies aids in classifying novel peptides and enzymes and also in understanding the biosynthetic pathways. Genome shuffling is a high-throughput screening approach to improve the development of SMs by incorporating genomic recombination. Transcriptionally silent or lower level BGCs can be triggered by artificially knocking promoter of target BGC. Additionally, bioinformatic tools like antiSMASH, ClustScan, NAPDOS, and ClusterFinder are effective in identifying BGCs of existing class for annotation in genomes. This review summarizes the significance of BGCs and the different approaches for detecting and elucidating BGCs from marine microbes.

摘要

海洋微生物通过产生不同的生物活性代谢物,在遗传上进化以适应不同的盐度、温度、pH 值和其他应激因素。这些微生物次生代谢物(SMs)是新颖的,具有高潜力,可以用作先导分子。微生物基因组测序表明,它们具有产生比标准体外培养条件下观察到的更多新型生物活性代谢物的能力。微生物基因组具有负责 SM 组装的特定区域,称为生物合成基因簇(BGCs),它们拥有编码生成 SM 所需的不同酶的所有必要基因。为了增加微生物的化学多样性并激活这些基因簇,开发了各种工具和技术。功能基因表达研究的宏基因组学有助于对新型肽和酶进行分类,并了解生物合成途径。基因组改组是一种高通量筛选方法,通过整合基因组重组来提高 SM 的开发。通过人为敲除目标 BGC 的启动子,可以触发转录沉默或低水平 BGC。此外,反 SMASH、ClustScan、NAPDOS 和 ClusterFinder 等生物信息学工具可有效识别现有类别 BGC 的注释基因组。本文综述了 BGC 的重要性以及从海洋微生物中检测和阐明 BGC 的不同方法。

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