Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Kiep, L.; Göhl, M.; Schmidt, J.; Seifert, K.;Studies on the Biotransformation of Veratric Acid, a Human Metabolite of Mebeverine, by Using the Incubated Hen’s EggDrug Res.65500-504(2015)DOI: 10.1055/s-0034-1390457
Metabolism studies with selected test substances have shown that a model on the basis of the incubated hen’s egg is suitable as a supplement to animal experimentation. Because of its 3,4-dimethoxyphenyl structure veratric acid (3,4-dimethoxybenzoic acid), a known human metabolite of mebeverine, was chosen as model substance for the present investigations and the parent compound as well as 4-hydroxy-3-methoxybenzoic acid were identified as main metabolites. The absence of 3-hydroxy-4-methoxybenzoic acid lets conclude that the O-demethylation takes place exclusively at the p-methoxyl function. In addition, 3,3’,4,4’-tetramethoxy-l-ornithuric acid (2,5-bis-(3,4-dimethoxybenzoylamino)pentanoic acid) and its O-desmethyl derivative could be characterized as further metabolites. So far an amino acid conjugate has not been described after veratric acid administration in a vertebrate. There were no indications for the appearance of 3,4-dihydroxybenzoic acid in the veratric acid metabolism. This was confirmed by corresponding studies having the isomeric guaiacol acids as precursor. Furthermore, it could be proved that in ovo the O-methylation of 3,4-dihydroxybenzoic acid occurs regioselective at the m-hydroxyl group. The results which broaden the knowledge on the metabolic fate of veratric acid are discussed in comparison with those in mammals. The metabolites were identified by GC-MS, ESI-HRMS and LC/ESI-MS/MS. The structure of the synthesized reference substance was confirmed by MS, 1H and 13C NMR spectral data.
Publikation
Schröder, G.; Unterbusch, E.; Kaltenbach, M.; Schmidt, J.; Strack, D.; De Luca, V.; Schröder, J.;Light-induced cytochrome P450-dependent enzyme in indole alkaloid biosynthesis: tabersonine 16-hydroxylaseFEBS Lett.45897-102(1999)DOI: 10.1016/S0014-5793(99)01138-2
Vinblastine and vincristine are two medically important bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle). Attempts at production in cell cultures failed because a part of the complex pathway was not active, i.e. from tabersonine to vindoline. It starts with tabersonine 16-hydroxylase (T16H), a cytochrome P450-dependent enzyme. We now show that T16H is induced in the suspension culture by light and we report the cloning of the cDNA. The enzyme was expressed in Escherichia coli as translational fusion with the P450 reductase from C. roseus, and the reaction product was identified by mass spectrometry. The protein (CYP71D12) shares 47–52% identity with other members of the CYP71D subfamily with unknown function. The induction by light was strongly enhanced by a nutritional downshift (transfer into 8% aqueous sucrose). We discuss the possibility that the entire pathway to bisindoles can be expressed in suspension cultures.