Microbial enzymes and associated biotransformations
| Microbial Enzyme/Pathway | Substrate Class | Examples | Biotransformation | Comment | Reference |
|---|---|---|---|---|---|
| β-Glucuronidase | Pharmaceutical | Irinotecan (colorectal cancer drug), Diclofenac, Indomethacin (NSAIDs) | Glucuronide hydrolysis | Irinotecan is converted to SN-38-G by the host and converted back into cytotoxic SN-38 in intestine with associated gastrointestinal side effects; example of enterohepatic cycling | Wallace et al., 2010; Saitta et al., 2014 |
| Endogenous | Serotonin dopamine | Asano et al., 2012; Hata et al., 2017 | |||
| Environmental pollutant | Nitrotoluene | Claus et al., 2016 | |||
| Dietary | IQ | Genotoxic/Carcinogenic compound formed in meat and fish during cooking | Humblot et al., 2007 | ||
| Azoreductase | Pharmaceutical | Sulfasalazine (IBD medication) | Azo bond reduction | Sulfasalazine is prodrug converted to the active agent 5-ASA by gut microbes | Peppercorn and Goldman, 1972b |
| Nitroreductase | Pharmaceutical | Bromazepam, Clonazepam, Nitrazepam (Benzodiazepines) | Nitro reduction | Antibiotic pretreatment can abolish enzyme activity; Nitrazepam is metabolized into 7-aminonitrazepam, which undergoes host hepatic metabolism into a teratogen | Elmer and Remmel, 1984; Fujii et al., 1987; Takeno and Sakai, 1991 |
| Cardiac glycoside reductase | Pharmaceutical | Digoxin (Cardiovascular) | Reduction | Reaction contingent on the correct strain of E. lentum and inhibited by dietary arginine | Haiser et al., 2013 |
| Tryptophanase | Dietary | Tryptophan | Deamination | Production of indole, which may have a role as an interspecies and interkingdom signaling molecule | Lee et al., 2015 |
| Glycyl radical enzymes (choline TMA-lyase) | Dietary | Choline | C-N bond cleavage elimination/oxidation | Production of TMA, associated with atherosclerosis and cardiovascular disease following host production of TMAO | Wang et al., 2011; Koeth et al., 2013; Craciun et al., 2014 |
| Carnitine oxygenase (Rieske-type oxygenase/reductase) | Dietary | Carnitine | Oxidation/Reduction | Production of TMA, associated with atherosclerosis and cardiovascular disease following host production of TMAO | Koeth et al., 2013; Zhu et al., 2014 |
| Saccharolytic pathways; butyryl-CoA:acetate CoA transferase | Dietary | Indigestible polysaccharides | Fermentation | Production of short chain fatty acids | Morrison and Preston, 2016 |
| Unknown | Pharmaceutical | Lovastatin | Hydroxylation | Metabolite formation reduced following antibiotic treatment | Yoo et al., 2014 |
| Decarboxylase | Dietary | L-tyrosine | Removal of carboxyl group | Bacterial production of p-cresol, which is sulfated by the host. P-cresol competes with acetaminophen for sulfation. | Smith and Macfarlane, 1997; Clayton et al., 2009; Dawson et al., 2011 |
| Linoleate isomerase | Dietary | Linoleic acid | Conjugation | Production of conjugated linoleic acid from food-derived lactobacilli | Yang et al., 2014 |
| Unknown | Pharmaceutical | L-Dopa | p-Dehydroxulation/Decarboxylation | L-Dopa can also bind to H. pylori; food-associated strain of L. brevis expresses tyrosine decarboxylase | Bergmark et al., 1972; Goldin et al., 1973; Niehues and Hensel, 2009; Zhang and Ni, 2014 |
| Unknown | Dietary | Caffeic acid | Reduction and dehydoxylation | Present in high levels in herbs such as thyme | Peppercorn and Goldman, 1972a |
| Phosphorylysases | Pharmaceutical | Sorivudine | Hydrolysis | Bromovinyluracil produced is metablized by the host to an inhibitor of host dihydropyrimidine dehydrogenase, leading to increased concentrations of 5-FU (anticancer drug) | Nakayama et al., 1997 |
| Unknown | Dietary | Melamine | Hydrolysis | Conversion to cyanuric acid, which cocrystallizes with melamine in kidneys | Zheng et al., 2013 |
| N-acyl synthase | Dietary | Oleic acid | Acylation | Products are able to modulate GPCRs | Cohen et al., 2017 |
| Peptide synthetase | Dietary | Amino acids | Peptide bond formation | Dipeiptide aldehyde produced can inhibit human cathepsins L | Guo et al., 2017 |
| Uracil phosphoribosyltransferase | Pharmaceutical | 5-FU | Phosphorylation | 5-fluorouridine monophospate produced is RNA damaging | Garcia-Gonzalez et al., 2017; Scott et al., 2017 |
| Bile salt hydrolyase | Dietary | Bile acids | Deconjugation | Further metabolism by 7 α dehydroxylase important | Joyce et al., 2014 |
GPCRs, G protein–coupled receptors.