Biocatalysis of Bioactive Taxanes

 

Executive Summary

 

Chemotherapy drugs are critical for effective patient cancer care. Unfortunately, the pharmaceutical industry has encountered several instances where it has not been able to supply sufficient quantities of important chemotherapy drugs due to manufacturing problems. Michigan State University researchers have discovered a novel, faster way of producing producing important drugs such as paclitaxel (Taxol®), cabazitaxel (Jevtana®) and docetaxel (Taxotere®) using biocatalysis. The process allows a more streamlined and faster in vitro synthesis that allows quickly ramp up the production during shortages, ensuring the pharmaceutical supply.

 

Description of Technology

 

The technology involves 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 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

  • Cancer drugs (breast, ovarian, lung, esophageal, pancreatic, bladder, prostate colon, stomach, etc.) 
  • Commercial potential for experimental precursors in research market

 

Patent Status:

 

Issued patents US 9,732,365; US 10,501,764

 

Licensing Rights Available

 

Full licensing rights available

 

 

Publications

 

Feb 2017 Biochemistry article

Oct 2017 Biochemistry article

 

Inventors: Dr. Kevin Walker

 

Tech ID: TEC2012-0076

Patent Information: