Metagenomics ‐ the next structural frontier

Abstract

Metagenomics aims to analyze, reconstruct and characterize how microbial communities organize and evolve their collective genomes to thrive in the environments they co‐habit. Human microbiomes harbor a large number of microbial species, many of which are uncharacterized or unculturable. The human gut microbiome represents a highly complex microbial community that has a significant impact on human physiology. This microbiome is believed to significantly enhance the metabolism of amino acids, carbohydrates, xenobiotics, methanogenesis, biosynthesis of vitamins and other compounds. Therefore, microbiomes represent a potential pool of genes coding for novel proteins and functions. The Protein Structure Initiative (PSI) human gut microbiome pilot project has been initiated with emphasis on the guts of healthy and diseased individuals. The PSI is well positioned to study proteins from microbiomes, and its high throughput protein production and structure determination pipelines are well suited to the microbial proteins that emanate from these projects. We have analyzed gut metagenomic data to identify novel, previously uncharacterized, human microbiome‐specific protein families. A set of reagent genomes was used to extract genes from gut microbiome and a number of structures from normal and enteric microflora have been determined. The structural and functional results will be discussed. This work was supported by National Institutes of Health Grant GM074942 and by the U.S. Department of Energy, OBER, under contract DE‐AC02‐06CH11357.