Engineered enzymes for chemical production.

In order to enable competitive manufacturing routes, most biocatalysts must be tailor-made for their processes. Enzymes from nature rarely have the combined properties necessary for industrial chemical production such as high activity and selectivity on non-natural substrates and toleration of high concentrations of organic media over the wide range of conditions (decreasing substrate, increasing product concentrations, solvents, etc.,) that will be present over the course of a manufacturing process. With the advances in protein engineering technologies, a variety of enzyme properties can be altered simultaneously, if the appropriate screening parameters are employed. Here we discuss the process of directed evolution for the generation of commercially viable biocatalysts for the production of fine chemicals, and how novel approaches have helped to overcome some of the challenges.

[1]  John C Whitman,et al.  Improving catalytic function by ProSAR-driven enzyme evolution , 2007, Nature Biotechnology.

[2]  Manfred T Reetz,et al.  Addressing the Numbers Problem in Directed Evolution , 2008, Chembiochem : a European journal of chemical biology.

[3]  K. Hungerbühler,et al.  Comparison of Four Technical Syntheses of Ethyl (R)‐2‐Hydroxy‐4‐Phenylbutyrate , 2004 .

[4]  Andreas Liese,et al.  Biocatalytic ketone reduction—a powerful tool for the production of chiral alcohols—part I: processes with isolated enzymes , 2007, Applied Microbiology and Biotechnology.

[5]  Sung-Hun Nam,et al.  Design and Evolution of New Catalytic Activity with an Existing Protein Scaffold , 2006, Science.

[6]  Loren L Looger,et al.  Computational Design of a Biologically Active Enzyme , 2004, Science.

[7]  Thomas E. Ferrin,et al.  Designed divergent evolution of enzyme function , 2006, Nature.

[8]  Nicholas J Turner,et al.  Directed evolution of enzymes for applied biocatalysis. , 2003, Trends in biotechnology.

[9]  Manfred T Reetz,et al.  Iterative saturation mutagenesis (ISM) for rapid directed evolution of functional enzymes , 2007, Nature Protocols.

[10]  Claes Gustafsson,et al.  Optimizing the search algorithm for protein engineering by directed evolution. , 2003, Protein engineering.

[11]  Christophe Boesch,et al.  Comparing Social Skills of Children and Apes , 2008, Science.

[12]  B. Stoddard,et al.  Computational Thermostabilization of an Enzyme , 2005, Science.