Microbial enzymes and associated biotransformations

Microbial Enzyme/PathwaySubstrate ClassExamplesBiotransformationCommentReference
β-GlucuronidasePharmaceuticalIrinotecan (colorectal cancer drug), Diclofenac, Indomethacin (NSAIDs)Glucuronide hydrolysisIrinotecan 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 cyclingWallace et al., 2010; Saitta et al., 2014
EndogenousSerotonin dopamineAsano et al., 2012; Hata et al., 2017
Environmental pollutantNitrotolueneClaus et al., 2016
DietaryIQGenotoxic/Carcinogenic compound formed in meat and fish during cookingHumblot et al., 2007
AzoreductasePharmaceuticalSulfasalazine (IBD medication)Azo bond reductionSulfasalazine is prodrug converted to the active agent 5-ASA by gut microbesPeppercorn and Goldman, 1972b
NitroreductasePharmaceuticalBromazepam, Clonazepam, Nitrazepam (Benzodiazepines)Nitro reductionAntibiotic pretreatment can abolish enzyme activity; Nitrazepam is metabolized into 7-aminonitrazepam, which undergoes host hepatic metabolism into a teratogenElmer and Remmel, 1984; Fujii et al., 1987; Takeno and Sakai, 1991
Cardiac glycoside reductasePharmaceuticalDigoxin (Cardiovascular)ReductionReaction contingent on the correct strain of E. lentum and inhibited by dietary arginineHaiser et al., 2013
TryptophanaseDietaryTryptophanDeaminationProduction of indole, which may have a role as an interspecies and interkingdom signaling moleculeLee et al., 2015
Glycyl radical enzymes (choline TMA-lyase)DietaryCholineC-N bond cleavage elimination/oxidationProduction of TMA, associated with atherosclerosis and cardiovascular disease following host production of TMAOWang et al., 2011; Koeth et al., 2013; Craciun et al., 2014
Carnitine oxygenase (Rieske-type oxygenase/reductase)DietaryCarnitineOxidation/ReductionProduction of TMA, associated with atherosclerosis and cardiovascular disease following host production of TMAOKoeth et al., 2013; Zhu et al., 2014
Saccharolytic pathways; butyryl-CoA:acetate CoA transferaseDietaryIndigestible polysaccharidesFermentationProduction of short chain fatty acidsMorrison and Preston, 2016
UnknownPharmaceuticalLovastatinHydroxylationMetabolite formation reduced following antibiotic treatmentYoo et al., 2014
DecarboxylaseDietaryL-tyrosineRemoval of carboxyl groupBacterial 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 isomeraseDietaryLinoleic acidConjugationProduction of conjugated linoleic acid from food-derived lactobacilliYang et al., 2014
UnknownPharmaceuticalL-Dopap-Dehydroxulation/DecarboxylationL-Dopa can also bind to H. pylori; food-associated strain of L. brevis expresses tyrosine decarboxylaseBergmark et al., 1972; Goldin et al., 1973; Niehues and Hensel, 2009; Zhang and Ni, 2014
UnknownDietaryCaffeic acidReduction and dehydoxylationPresent in high levels in herbs such as thymePeppercorn and Goldman, 1972a
PhosphorylysasesPharmaceuticalSorivudineHydrolysisBromovinyluracil 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
UnknownDietaryMelamineHydrolysisConversion to cyanuric acid, which cocrystallizes with melamine in kidneysZheng et al., 2013
N-acyl synthaseDietaryOleic acidAcylationProducts are able to modulate GPCRsCohen et al., 2017
Peptide synthetaseDietaryAmino acidsPeptide bond formationDipeiptide aldehyde produced can inhibit human cathepsins LGuo et al., 2017
Uracil phosphoribosyltransferasePharmaceutical5-FUPhosphorylation5-fluorouridine monophospate produced is RNA damagingGarcia-Gonzalez et al., 2017; Scott et al., 2017
Bile salt hydrolyaseDietaryBile acidsDeconjugationFurther metabolism by 7 α dehydroxylase importantJoyce et al., 2014
  • GPCRs, G protein–coupled receptors.