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Researchers advance biosynthesis of potent anti-cancer drug Taxol
Date:9/30/2010

ermediates, taxadiene and taxadien-5alpha-ol.

The researchers partitioned the taxadiene metabolic pathway into two modules: the intracellular supply of substrates, or precursors, that must be present within the E. coli cell before Taxol can be produced (the upstream pathway) and the biosynthetic steps needed to make the first two Taxol intermediates (the downstream pathway).

This modular approach allowed manipulation of the many variables in each pathway to achieve the right balance to optimize production of the two intermediates. It effectively "unlocked" unprecedented production levels of early-stage Taxol intermediates through E. coli.

The team reported producing more than 1 gram of taxadiene per liter of production culture a level that was 1,000 times greater than had previously been reported using E. coli as a host and 15,000 times more than the study's initial production levels prior to balancing the upstream and downstream modular pathways. For the first time, the second Taxol precursor, taxadiene-5alpha-ol, was produced from E. coli.

The researchers caution that significant work is still needed in order to complete the synthesis of a Taxol precursor suitable for commercial production and potentially replace the current plant-based production process with a more efficient operation based upon microbial biosynthesis. Such an approach could also be applied to production of chemicals and fuels microbially derived from renewable resources.

"Though this is only a first step, it is a very promising development and certainly supports this approach and its potential," said Pfeifer.


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Contact: Kim Thurler
kim.thurler@tufts.edu
617-627-3175
Tufts University
Source:Eurekalert

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