Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme
This work has identified a gene cluster responsible for anaerobic choline degradation within the genome of a sulfate-reducing bacterium and verified its function using both a genetic knockout strategy and heterologous expression in Escherichia coli.
The Genetic and Molecular Basis for Sunscreen Biosynthesis in Cyanobacteria
The identification of a MAA biosynthetic gene cluster in a cyanobacterium and the discovery of analogous pathways in other sequenced organisms are reported.
Characterization and Detection of a Widely Distributed Gene Cluster That Predicts Anaerobic Choline Utilization by Human Gut Bacteria
This work established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches and developed a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA.
Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta
- Henry J. Haiser, D. B. Gootenberg, K. Chatman, G. Sirasani, E. Balskus, P. Turnbaugh
- Biology, MedicineScience
- 19 July 2013
The inactivation of the cardiac drug digoxin by the gut Actinobacterium Eggerthella lenta is dissect, revealing a cytochrome-encoding operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome.
Minimum Information about a Biosynthetic Gene cluster.
This work proposes the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard, to facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters.
Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
The major proposed pathway involves an initial decarboxylation of l-dopa to dopamine, followed by conversion of dopamine to m-tyramine by means of a distinctly microbial dehydroxylation reaction.
Characterization of choline trimethylamine-lyase expands the chemistry of glycyl radical enzymes.
In vitro characterization of CutC and its activating protein CutD is described and it is established that CutC is a GRE of unique function and a molecular marker for anaerobic choline metabolism.
Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction.
The human gut bacterial genotoxin colibactin alkylates DNA
Interestingly, the isolation and structural characterization of metabolites from mutant strains of pks+ E. coli revealed that colibactin likely contains a cyclopropane ring, a reactive structural motif found in DNA alkylating natural products, which led to hypothesize that colIBactin may covalently modify DNA.
A prodrug resistance mechanism is involved in colibactin biosynthesis and cytotoxicity.
- C. A. Brotherton, E. Balskus
- Biology, ChemistryJournal of the American Chemical Society
- 20 February 2013
The biochemical characterization of the prodrug synthesis, elongation, and cleavage enzymes from the colibactin biosynthetic pathway is described and suggests that cytotoxicity requires amide bond cleavage.