- Natural Product Diversification by One-Step Biocatalysis using Human P450 3A4
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Efficient synthetic techniques for the diversification of natural products are incremental for drug discovery processes of the pharmaceutical industry because these complex bioactive compounds often require an adjustment of properties. Human liver P450 3A4, key player of the body's detoxification system and decisive factor of a drug's metabolic fate, is renowned for its broad substrate scope including many natural products. In this study, we investigated the synthetic potential of human P450 3A4 for the diversification of natural product classes and isolated the produced metabolites of six selected natural products at a preparative 100-mg scale. Aided by efficient expression levels in P. pastoris, this whole-cell biocatalyst was found to be highly effective at the intended job allowing the identification of a total of 31 authentic human metabolites, many of them for the first time. By revealing an unprecedented degree of diversification, this study extends the synthetic repertoire for efficient enzymatic natural product modification in a one-step fashion and adds a completely new view to an old enzyme traditionally used for inhibition and toxicology studies.
- Fessner, Nico D.,Grimm, Christopher,Srdi?, Matic,Weber, Hansj?rg,Kroutil, Wolfgang,Schwaneberg, Ulrich,Glieder, Anton
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- Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a
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The metabolism of papaverine, the opium benzylisoquinoline alkaloid, with Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968 and Cunninghamella echinulate ATCC 1382 has resulted in O-demethylation, O-methylgluc
- Eliwa, Duaa,Albadry, Mohamed A.,Ibrahim, Abdel-Rahim S.,Kabbash, Amal,Meepagala, Kumudini,Khan, Ikhlas A.,El-Aasr, Mona,Ross, Samir A.
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- Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A
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A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A
- Zhang, Zhanbin,Lu, Xiaoxia,Xu, Jinbin,Rothfuss, Justin,MacH, Robert H.,Tu, Zhude
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p. 3986 - 3995
(2011/10/31)
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