Researchers at Codexis say they have developed a custom biocatalyst that showed a 4,000-fold productivity increase over the natural enzyme. The resulting biocatalyst is used to manufacture a key building block of atorvastatin, the active ingredient in Pfizer’s cholestrol lowering drug, Lipitor.
“Faced with a need to improve manufacturing processes, the pharmaceutical industry is increasingly turning to the use of biocatalysts, or enzymes, to enhance manufacturing efficiency and reduce environmental waste,” explains John Grate, Ph.D., Codexis senior vp, R&D and CTO.
“Historically, biocatalysts have been viewed as a limited option for commercial manufacturing. This was due to the typically low productivity of most available naturally-occurring enzymes. This is changing, as the technology has advanced for creating customized biocatalysts, which improve on what is available from nature.
“In this study, Codexis researchers showed that we can substantially accelerate development of customized biocatalysts with greatly increased productivity, which can enable new, more efficient pharmaceutical chemical manufacturing processes.”
The Codexis research team applied proprietary bioinformatics software to model relationships between protein sequence and protein activity (ProSAR) and used this information to guide the optimization of the custom biocatalyst using its directed molecular evolution technology.