B-B.02: Metagenome-guided discovery of novel laccases for biotransformation by geographically-diverse human gut microbiota
Keywords
metagenomics, reproducible omics workflows, enzyme discovery, gut microbiome, human microbiome
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The human gut microbiome represents a vast untapped reservoir of microbial functional diversity, including novel enzymatic functionality. Such functions can be screened by leveraging the large quantities of existing gut metagenome sequencing data to characterize enzyme diversity. We applied this approach to mine metagenomes for laccase enzymes relevant for microbial biotransformation of fluorinated compounds with the aim of understanding potential effects of these biotransformations on human health. Through a multi-study analysis of 1578 human gut metagenomes with the MOSHPIT metagenomics distribution, we found that laccase-coding genes are widely distributed in the human gut microbiome. We identified a significant association between both the abundance of laccase-coding genes and the phylogeny of laccase amino acid sequences with the degree of urbanization along a gut microbiome gradient from hunter-gatherer societies to highly industrialized urban populations. In an experimental follow-up, we heterologously expressed and tested gut bacterial laccases with a chemical mediator system as well as fluorinated pharmaceuticals and agrochemicals to validate the predicted activity, demonstrating successful depletion of cyflumetofen, fluazinam, and bisphenol AF by a laccase. By linking global gut metagenomes with activity assays, this work demonstrates the potential of mining public metagenome databases for novel enzymes with biotechnological and therapeutic applications.
Co-authors: Yaochun Yu, Aaron Grawe, James K. Christenson, Serina L. Robinson, Nicholas A. Bokulich
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