Biocatalysis of Bioactive Taxanes

 

Executive Summary

 

A shortage of the chemotherapeutic paclitaxel (Taxol®) due to an unreliable pharmaceutical supply chain lead researchers at Michigan State University (MSU) to discover and propose a novel, faster way of producing paclitaxel and related anti-cancer drugs: Using a biocatalytic process, Taxol can now be produced in a more streamlined and faster in vitro synthesis process to quickly ramp up the production during shortages, ensuring the pharmaceutical supply for many breast cancer patients as well as patients with ovarian, lung, bladder, and colon cancers.

This biocatalysis method also provides a streamlined in vitro enzymatic process for the production of taxane drugs such as cabazitaxel (Jevtana®) and docetaxel (Taxotere®), reducing the use of petroleum-based solvents such as hexanes and tetrahydrofuran and eliminating the use of pyrophoric reagents such as n-butyllithium.

 

Description of Technology

 

Researchers at MSU discovered a key enzyme, Tyrocidine Synthetase A (TycA: PheAT), which catalyzes the production of phenylisoserinyl CoA thioester, a key precursor to anti-cancer taxane drugs. A second enzyme, phenylpropanoyltransferase (BAPT), is used with PheAT in an enzyme cascade reaction to produce further taxane intermediates. This biocatalysis method provides a simple, streamlined in vitro enzymatic process for the production of taxane drugs such as cabazitaxel (Jevtana®), docetaxel (Taxotere®), as well as paclitaxel (Taxol®). Water-based buffer steps reduce use of petroleum-based solvents such as hexanes and tetrahydrofuran. The proposed method also eliminates the use of pyrophoric reagents such as n-butyllithium in the production of cabazitaxel. Lab scale production yields have shown far greater results than the calculated theoretical yields.

 

Key Benefits

  • More efficient, faster, and more flexible synthesis of paclitaxel and related anti-cancer drugs
  • More streamlined production process
  • Controlled environment, in vitro synthesis possible
  • No harsh organic solvents used, greener production

 

Applications

  • Global cancer drug market
  • Commercial potential for experimental precursors in research market

 

Patent Status:

 

Issued patent, patent number US 9,732,365

 

Licensing Rights Available

 

Full licensing rights available

 

Inventors: Kevin Walker

 

Tech ID: TEC2012-0076

 

Temporary Contact

 

Nina (Isi) Davis, Technology Marketing Manager, email: davisnin@msu.edu, phone (direct): (517) 884-1829

 

Patent Information:

Category(s):

For Information, Contact:

Randy Ramharack
Technology Manager
Michigan State University
ramharac@msu.edu
Inventors:
Kevin Walker
Keywords: