Choline trimethylamine-lyase (CutC) (CutC)

Choline trimethylamine-lyase (CutC) is a microbial glycyl radical enzyme that catalyzes the anaerobic cleavage of choline into trimethylamine (TMA) and acetaldehyde (Craciun & Balskus, 2012, PNAS). This enzyme is primarily found in various species of the human gut microbiota and represents the rate-limiting step in the production of TMA, which is subsequently absorbed and converted by host hepatic flavin-containing monooxygenases into trimethylamine N-oxide (TMAO) (Tang et al., 2013, NEJM). Elevated systemic levels of TMAO are strongly linked to the pathogenesis of cardiovascular diseases, including atherosclerosis, thrombosis, and heart failure, as well as the progression of chronic kidney disease (Wang et al., 2011, Nature). CutC has emerged as a novel therapeutic target for reducing TMAO levels through a "drugging the microbiome" approach that does not rely on traditional antibiotics. Small molecule inhibitors, such as iodomethylcholine (IMC) and fluoromethylcholine (FMC), act as potent, non-lethal inhibitors that significantly lower systemic TMAO levels and reduce atherosclerotic plaque formation in preclinical models (Roberts et al., 2018, Nature Medicine). These inhibitors are designed to selectively target microbial metabolism while minimizing the risk of gut dysbiosis or toxicity to the host.

Other names

Choline lyaseCholine-trimethylamine lyaseCutCCholine-TMA lyase

Inhibition of the microbial enzyme CutC to prevent the conversion of dietary choline into trimethylamine (TMA), thereby reducing systemic levels of the pro-atherogenic metabolite trimethylamine N-oxide (TMAO).