Metabolism of Pharmaceuticals in Plants
and Their Associated Microbiota
Andrés Sauvêtre, Peter Eichhorn, and Sandra Pérez
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
2 Human Drug-Metabolizing Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
2.1 Phase I Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
2.2 Phase II Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
3 Drug Metabolism in Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
3.1 Phase I Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
3.2 Phase II Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
3.3 Phase III Plant Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
4 Plant Models for the Study of Pharmaceutical Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
4.1 Whole Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
4.2 In Vitro Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
4.3 Examples of Method Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
4.4 Hairy Roots as Model for the Study of Root Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
5 Role of Microbiome in Pharmaceutical Metabolism and Plant-Microbe Interactions . . . . . 249
5.1 The Rhizosphere Is a Hot Spot for Pharmaceutical Metabolism and Metabolite
Exchange Between Plant and Microorganisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
5.2 Endophytic Bacteria Can Enhance Degradation of Pharmaceuticals in Plants . . . . . . 253
6 Conclusion and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Abstract With the increasing use of wastewater for irrigation of farmland, and thus
the potential uptake and translocation of pharmaceuticals and their metabolites in
crops, concerns about food safety are growing. After their uptake, plants are able to
metabolize drugs to phase I, phase II, and phase III metabolites. Phase I reactions
closely resemble those encountered in human drug metabolism, including
A. Sauvêtre (*)
UMR HydroSciences Montpellier, Montpellier University, Montpellier, France
e-mail: andre.sauvetre@umontpellier.fr
P. Eichhorn and S. Pérez
ENFOCHEM, Department of Environmental Chemistry, Institute of Environmental Assessment
and Water Research, Barcelona, Spain
Sandra Pérez Solsona, Nicola Montemurro, Serge Chiron, and Damià Barceló (eds.),
Interaction and Fate of Pharmaceuticals in Soil-Crop Systems: The Impact of
Reclaimed Wastewater, Hdb Env Chem (2021) 103: 221–264, DOI 10.1007/698_2020_607,
© Springer Nature Switzerland AG 2020, Published online: 8 September 2020
221
and Their Associated Microbiota
Andrés Sauvêtre, Peter Eichhorn, and Sandra Pérez
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
2 Human Drug-Metabolizing Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
2.1 Phase I Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
2.2 Phase II Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
3 Drug Metabolism in Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
3.1 Phase I Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
3.2 Phase II Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
3.3 Phase III Plant Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
4 Plant Models for the Study of Pharmaceutical Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
4.1 Whole Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
4.2 In Vitro Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
4.3 Examples of Method Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
4.4 Hairy Roots as Model for the Study of Root Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
5 Role of Microbiome in Pharmaceutical Metabolism and Plant-Microbe Interactions . . . . . 249
5.1 The Rhizosphere Is a Hot Spot for Pharmaceutical Metabolism and Metabolite
Exchange Between Plant and Microorganisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
5.2 Endophytic Bacteria Can Enhance Degradation of Pharmaceuticals in Plants . . . . . . 253
6 Conclusion and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Abstract With the increasing use of wastewater for irrigation of farmland, and thus
the potential uptake and translocation of pharmaceuticals and their metabolites in
crops, concerns about food safety are growing. After their uptake, plants are able to
metabolize drugs to phase I, phase II, and phase III metabolites. Phase I reactions
closely resemble those encountered in human drug metabolism, including
A. Sauvêtre (*)
UMR HydroSciences Montpellier, Montpellier University, Montpellier, France
e-mail: andre.sauvetre@umontpellier.fr
P. Eichhorn and S. Pérez
ENFOCHEM, Department of Environmental Chemistry, Institute of Environmental Assessment
and Water Research, Barcelona, Spain
Sandra Pérez Solsona, Nicola Montemurro, Serge Chiron, and Damià Barceló (eds.),
Interaction and Fate of Pharmaceuticals in Soil-Crop Systems: The Impact of
Reclaimed Wastewater, Hdb Env Chem (2021) 103: 221–264, DOI 10.1007/698_2020_607,
© Springer Nature Switzerland AG 2020, Published online: 8 September 2020
221