ArticleChemistry (Weinheim an der Bergstrasse, Germany)2009
A panel of cytochrome P450 BM3 variants to produce drug metabolites and diversify lead compounds.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 143 citations in OpenAlex.
- Expanding the Biocatalytic Toolbox: A Singular P450 Enzyme Efficiently Produces Diverse Pharmaceutical Metabolites.ACS omega · 2026Article
- Article
- Stereoselective Biotransformation: Transfer of Learning to Advance Drug Metabolism and Biocatalysis.Angewandte Chemie (International ed. in English) · 2026Review
- Drug Metabolism by Engineered Toluene o-Xylene Monooxygenases of Pseudomonas sp. OX1.Biotechnology and bioengineering · 2026Article
- Cytochrome P450The Journal of biological chemistry · 2025Article
- Choose Your Own Adventure: A Comprehensive Database of Reactions Catalyzed by Cytochrome P450 BM3 Variants.ACS catalysis · 2024Review
- Electrochemical Late-Stage Functionalization.Chemical reviews · 2023Review
- Non-Native Site-Selective Enzyme Catalysis.Chemical reviews · 2023Review
- A preparative small-molecule mimic of liver CYP450 enzymes in the aliphatic C-H oxidation of carbocyclicProceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Versatile Biocatalyst of Cytochrome P450 CYP102A1: Structure, Function, and Engineering.Molecules (Basel, Switzerland) · 2023Review
- Current state and future perspectives of cytochrome P450 enzymes for C-H and C=C oxygenation.Synthetic and systems biotechnology · 2022Article
- Recent Advances in Biocatalysis for Drug Synthesis.Biomedicines · 2022Review
- A Perspective on Late-Stage Aromatic C-H Bond Functionalization.Journal of the American Chemical Society · 2022Article
- A Promiscuous Bacterial P450: The Unparalleled Diversity of BM3 in Pharmaceutical Metabolism.International journal of molecular sciences · 2021Review
- Late-stage C-H functionalization offers new opportunities in drug discovery.Nature reviews. Chemistry · 2021Review
- Kinetic Evidence for an Induced Fit Mechanism in the Binding of the Substrate Camphor by Cytochrome P450ACS catalysis · 2021Article
- Biotransformation: Impact and Application of Metabolism in Drug Discovery.ACS medicinal chemistry letters · 2020Article
- Advances in the study of drug metabolism - symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX).Drug metabolism reviews · 2020Review
- Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius rotula for toxicological studies on human cancer cells.AMB Express · 2020Article
- Methylene Oxidation of Alkyl Sulfates by Cytochrome P450ACS catalysis · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Herein we demonstrate that a small panel of variants of cytochrome P450 BM3 from Bacillus megaterium covers the breadth of reactivity of human P450s by producing 12 of 13 mammalian metabolites for two marketed drugs, verapamil and astemizole, and one research compound. The most active enzymes support preparation of individual metabolites for preclinical bioactivity and toxicology evaluations. Underscoring their potential utility in drug lead diversification, engineered P450 BM3 variants also produce novel metabolites by catalyzing reactions at carbon centers beyond those targeted by animal and human P450s. Production of a specific metabolite can be improved by directed evolution of the enzyme catalyst. Some variants are more active on the more hydrophobic parent drug than on its metabolites, which limits production of multiply-hydroxylated species, a preference that appears to depend on the evolutionary history of the P450 variant.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.