Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrated Program for Biological and Genome Sciences, And Departments of Biochemistry and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Opin Struct Biol. 2022 Aug;75:102416. doi: 10.1016/j.sbi.2022.102416. Epub 2022 Jul 13.
Metagenomic sequencing data provide a rich resource from which to expand our understanding of differential protein functions involved in human health. Here, we outline a pipeline that combines microbial whole genome sequencing with protein structure data to yield a structural metagenomics-informed atlas of microbial enzyme families of interest. Visualizing metagenomics data through a structural lens facilitates downstream studies including targeted inhibition and probe-based proteomics to define at the molecular level how different enzyme orthologs impact in vivo function. Application of this pipeline to gut microbial enzymes like glucuronidases, TMA lyases, and bile salt hydrolases is expected to pinpoint their involvement in health and disease and may aid in the development of therapeutics that target specific enzymes within the microbiome.
宏基因组测序数据为我们提供了丰富的资源,有助于我们深入了解与人类健康相关的差异蛋白功能。在这里,我们概述了一个结合微生物全基因组测序和蛋白质结构数据的工作流程,生成了一个结构宏基因组学指导的微生物酶家族图谱。通过结构视角可视化宏基因组学数据有助于下游研究,包括靶向抑制和基于探针的蛋白质组学,以在分子水平上定义不同酶同源物如何影响体内功能。将该工作流程应用于肠道微生物酶,如葡萄糖醛酸酶、TMA 裂解酶和胆盐水解酶,有望确定它们在健康和疾病中的作用,并可能有助于开发针对微生物组中特定酶的治疗方法。