Biocatalysis of Paclitaxel
Importance of Paclitaxel Chemotherapy
Paclitaxel |
Nanoparticle Albumin-bound Paclitaxel in Independent Clinical Trials ▪ Nab-paclitaxel (paclitaxel bound to albumin) enabled delivery of higher drug doses, resulting in higher effective concentration, with shorter infusion duration than with the solvent-based paclitaxel formulations. The Lancet Gastroenterology & Hepatology 2017, 2, 277. |
Current ~18-Step Biosynthesis of Paclitaxel in Plant Cell Cultures: The current fermentation method uses Taxus cells to produce paclitaxel. Many of theenzymes accept multiple substrates and produce multiple products. This creates a complex metabolic network of over 400 taxoids, which are difficult to separate.
Four-Enzyme Cascade Reaction to Paclitaxel:
Using PheAT and BadA (CoA Ligases), BAPT and BT (Acyltransferase)
Alternative Streamlined 4-Enzyme Cascade Reaction to Paclitaxel: As an alternative to make paclitaxel, we use regioselective biocatalysts (Taxus Acyltransferases (AT) of the BAHD Superfamily and Bacterial CoA Ligases) that streamline the production pipeline to the target pharmaceutical paclitaxel (Taxol). No taxane side products accumulate and cofactors (ATP and Coenzyme A) can be recycled.
Coupling acyltransferases with CoA ligases (below) provides a Green source of a taxane drug precursor.
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