Environmental activity-based protein profiling for function-driven enzyme discovery from natural communities

作者：Sabrina Ninck, Thomas Klaus, Tatiana V. Kochetkova, Sarah P. Esser, Leonard Sewald, Farnusch Kaschani, Christopher Bräsen, Alexander J. Probst, Ilya V. Kublanov, Bettina Siebers, Markus Kaiser · 发表于：Environmental Microbiome · 年份：2024 · DOI：10.1186/s40793-024-00577-2 · 被引用次数：6 · 研究领域：Advanced Proteomics Techniques and Applications、Enzyme Catalysis and Immobilization、Enzyme Production and Characterization

BACKGROUND: Microbial communities are important drivers of global biogeochemical cycles, xenobiotic detoxification, as well as organic matter decomposition. Their major metabolic role in ecosystem functioning is ensured by a unique set of enzymes, providing a tremendous yet mostly hidden enzymatic potential. Exploring this enzymatic repertoire is therefore not only relevant for a better understanding of how microorganisms function in their natural environment, and thus for ecological research, but further turns microbial communities, in particular from extreme habitats, into a valuable resource for the discovery of novel enzymes with potential applications in biotechnology. Different strategies for their uncovering such as bioprospecting, which relies mainly on metagenomic approaches in combination with sequence-based bioinformatic analyses, have emerged; yet accurate function prediction of their proteomes and deciphering the in vivo activity of an enzyme remains challenging. RESULTS: Here, we present environmental activity-based protein profiling (eABPP), a multi-omics approach that extends genome-resolved metagenomics with mass spectrometry-based ABPP. This combination allows direct profiling of environmental community samples in their native habitat and the identification of active enzymes based on their function, even without sequence or structural homologies to annotated enzyme families. eABPP thus bridges the gap between environmental genomics, correct function annotati...