ArticleScientific reports2015
Highly Efficient CYP167A1 (EpoK) dependent Epothilone B Formation and Production of 7-Ketone Epothilone D as a New Epothilone Derivative.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 31 citations in OpenAlex.
- Functional analysis of the whole CYPome and Fdxome ofEngineering microbiology · 2024Article
- Efficient stereoselective hydroxylation of deoxycholic acid by the robust whole-cell cytochrome P450 CYP107D1 biocatalyst.Synthetic and systems biotechnology · 2023Article
- Prokaryotic expression and characterization of artificial self-sufficient CYP120A monooxygenases.Applied microbiology and biotechnology · 2023Article
- Heterologous Expression of the Hot Pepper ABA 8'-Hydroxylase inJournal of microbiology and biotechnology · 2023Article
- Heterologous redox partners supporting the efficient catalysis of epothilone B biosynthesis by EpoK in Schlegelella brevitalea.Microbial cell factories · 2020Article
- Engineering cytochrome P450 enzyme systems for biomedical and biotechnological applications.The Journal of biological chemistry · 2020Review
- Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway.Journal of cancer research and clinical oncology · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since their discovery in the soil bacterium Sorangium cellulosum, epothilones have emerged as a valuable substance class with promising anti-tumor activity. Because of their benefits in the treatment of cancer and neurodegenerative diseases, epothilones are targets for drug design and pharmaceutical research. The final step of their biosynthesis - a cytochrome P450 mediated epoxidation of epothilone C/D to A/B by CYP167A1 (EpoK) - needs significant improvement, in particular regarding the efficiency of its redox partners. Therefore, we have investigated the ability of various hetero- and homologous redox partners to transfer electrons to EpoK. Hereby, a new hybrid system was established with conversion rates eleven times higher and Vmax of more than seven orders of magnitudes higher as compared with the previously described spinach redox chain. This hybrid system is the most efficient redox chain for EpoK described to date. Furthermore, P450s from So ce56 were identified which are able to convert epothilone D to 14-OH, 21-OH, 26-OH epothilone D and 7-ketone epothilone D. The latter one represents a novel epothilone derivative and is a suitable candidate for pharmacological tests. The results revealed myxobacterial P450s from S. cellulosum So ce56 as promising candidates for protein engineering for biotechnological production of epothilone derivatives.
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