A5071740181- Gut microbiota and health
- Microbial Natural Products and Biosynthesis
- Synthetic Organic Chemistry Methods
- Enzyme Catalysis and Immobilization
- Microbial Metabolic Engineering and Bioproduction
- Probiotics and Fermented Foods
- Metabolism and Genetic Disorders
- Clostridium difficile and Clostridium perfringens research
- Metalloenzymes and iron-sulfur proteins
- Carbohydrate Chemistry and Synthesis
- Genomics and Phylogenetic Studies
- Marine Sponges and Natural Products
- Reproductive tract infections research
- Photosynthetic Processes and Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Plant biochemistry and biosynthesis
- Bacterial Genetics and Biotechnology
- Microbial Community Ecology and Physiology
- Asymmetric Synthesis and Catalysis
- Folate and B Vitamins Research
- Diet and metabolism studies
- Cyclopropane Reaction Mechanisms
- Chemical Synthesis and Analysis
- CO2 Reduction Techniques and Catalysts
- Algal biology and biofuel production
Harvard University
2016-2025
Howard Hughes Medical Institute
2022-2025
Harvard University Press
2004-2025
Broad Institute
2017-2024
University of California, San Diego
2015
Scripps Institution of Oceanography
2015
Universidade do Porto
2015
Williams College
2002-2008
Center for Integrated Protein Science Munich
2008
Technical University of Munich
2008
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded biosynthetic gene clusters. Information about these clusters, is currently dispersed throughout the literature, making it difficult exploit. To facilitate consistent systematic deposition retrieval data on we propose Minimum a Biosynthetic Gene cluster (MIBiG) standard.
Choline and trimethylamine (TMA) are small molecules that play central roles in biological processes throughout all kingdoms of life. These ubiquitous metabolites linked through a single biochemical transformation, the conversion choline to TMA by anaerobic microorganisms. This metabolic activity, which contributes methanogenesis human disease, has been known for over century but eluded genetic characterization. We have identified gene cluster responsible degradation within genome...
Despite numerous examples of the effects human gastrointestinal microbiome on drug efficacy and toxicity, there is often an incomplete understanding underlying mechanisms. Here, we dissect inactivation cardiac digoxin by gut Actinobacterium Eggerthella lenta. Transcriptional profiling, comparative genomics, culture-based assays revealed a cytochrome-encoding operon up-regulated digoxin, inhibited arginine, absent in nonmetabolizing E. lenta strains, predictive microbiome. Pharmacokinetic...
The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, organisms, genes, enzymes responsible for this activity in patients their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway bacterial l-dopa metabolism. Conversion of dopamine a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed...
Certain Escherichia coli strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated colorectal cancer pathogenesis. However, colibactin's chemical structure and molecular mechanism underlying its genotoxic effects have remained unknown for more than decade. Here we combine an untargeted DNA adductomics approach with synthesis to identify characterize covalent modification from cell lines treated colibactin-producing E. Our data establish that colibactin...
Ultraviolet UV-A and UV-B radiation is harmful to living systems, causing damage biological macromolecules. An important strategy for dealing with UV exposure the biosynthesis of small-molecule sunscreens. Among such metabolites, mycosporine mycosporine-like amino acids (MAAs) are remarkable their wide phylogenetic distribution unique chemical structures. Here, we report identification a MAA biosynthetic gene cluster in cyanobacterium discovery analogous pathways other sequenced organisms....
Elucidation of the molecular mechanisms underlying human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with community as a whole to individual microorganisms activities. Anaerobic microbial choline metabolism, disease-associated pathway, exemplifies this challenge, specific responsible for transformation have not yet clearly identified. In study, we established link between bacterial gene cluster, utilization...
Significance This paper describes a pathway for anaerobic bacterial metabolism of taurine (2-aminoethanesulfonate), an abundant substrate in the human intestinal microbiota, by bacterium and opportunistic pathogen, Bilophila wadsworthia . converts to toxic metabolite hydrogen sulfide (H 2 S), activity associated with inflammatory bowel disease colorectal cancer. A critical enzyme this is isethionate sulfite-lyase, member glycyl radical family. catalyzes novel, radical-based C-S bond-cleavage...
Colibactin is a chemically unstable small-molecule genotoxin that produced by several different bacteria, including members of the human gut microbiome
Commensal Escherichia coli residing in the human gut produce colibactin, a small-molecule genotoxin of unknown structure that has been implicated development colon cancer. Colibactin biosynthesis is hypothesized to involve prodrug resistance strategy entails initiation via construction an N-terminal scaffold and late-stage cleavage this structural motif during product export. Here we describe biochemical characterization synthesis, elongation, enzymes from colibactin biosynthetic pathway. We...
The human gut microbiota plays a key role in pharmacology, yet the mechanisms responsible remain unclear, impeding efforts toward personalized medicine. We recently identified cytochrome-encoding operon common Actinobacterium Eggerthella lenta that is transcriptionally activated by cardiac drug digoxin. These genes represent predictive microbial biomarker for inactivation of Gnotobiotic mouse experiments revealed increased protein intake can limit inactivation. Here, we present biochemical...
Chemically guided functional profiling The big challenge posed by the microbiota living in or on humans is working out what they do for us. Microorganisms generate large quantities of peptides and proteins that may have profound systemic effects host. Levin et al. took microbial metagenome data used a combination bioinformatic tools to network clusters sequences enzymes sharing similar biological functions (see Perspective Glasner). Experiments verified these homology structural-chemical...
The recently identified glycyl radical enzyme (GRE) homologue choline trimethylamine-lyase (CutC) participates in the anaerobic conversion of to trimethylamine (TMA), a widely distributed microbial metabolic transformation that occurs human gut and is linked disease. proposed biochemical function CutC, C-N bond cleavage, represents new reactivity for GRE family. Here we describe vitro characterization CutC its activating protein CutD. We have observed CutD-mediated formation on using EPR...
Although the human gut microbiome plays a prominent role in xenobiotic transformation, most of genes and enzymes responsible for this metabolism are unknown. Recently, we linked two-gene ‘cardiac glycoside reductase’ (cgr) operon encoded by Actinobacterium Eggerthella lenta to inactivation cardiac medication plant natural product digoxin. Here, compared genomes 25 E. strains close relatives, revealing an expanded 8-gene cgr-associated gene cluster present all digoxin metabolizers absent...