Biohybrid catalysts in whole-cell systems for selective chemical reactions

Biohybrid catalysts in whole-cell systems for selective chemical reactions

Challenge

Biohybrid catalysts enable a variety of new selective reactions by combining successful principles of biocatalysis with those of homogeneous chemical catalysis. For example, biohybrid catalysts can combine metals not used in nature with the specific environment of proteins to achieve high selectivity. Biohybrid catalysts in whole-cell systems have the potential to be used in organic solvents as well and can be optimised for catalytic reactions by inexpensive and efficient methods of directed evolution. The use of whole cells protects the protein structure from denaturing conditions and does not require prior protein purification. So far, however, protein engineering of biohybrid catalysts in whole cells has been limited to soluble proteins in the periplasm. This approach is severely constrained by the limited uptake of metal complexes and substrates into the cells. In addition, most transition metal complexes are very sensitive to nucleophilic attacks by cellular components.

Solution

The whole-cell-based biohybrid catalyst system presented here enables chemical synthesis reactions in industrial scale for which isolated biohybrid catalysts are not desirable, especially for financial reasons. The biohybrid catalysts of the system are located in the outer membrane of bacteria such as E. coli and consist of a protein scaffold and an attached catalytic component (see figure). Membrane proteins of the outer cell membrane, e.g., proteins with a β-barrel structure such as FhuA and nitrobindin, act as scaffolds, and their large cavities allow for precise positioning of the catalytic complexes deep within their β-barrel structure. This leads to extensive control of the environment of the catalytic complexes through specifically exchangeable amino acids, thus controlling selectivity and activity. For example, organometallic compounds (such as ruthenium-containing Grubbs-Hoveyda catalysts) or organocatalysts act as catalytic components bound to the protein scaffold. Localising the biohybrid catalysts in the outer cell membrane avoids the problem of the membrane acting as a diffusion barrier while keeping deactivating nucleophiles (inside the cell) away from the catalytic components.

Advantage

• New cost-effective selective syntheses possible
• Protein engineering of the reaction environment
• Good steric control & maximum substrate accessibility to active components
• High selectivity and activity
• Simple purification & easy removal of metal complexes

Status

• Patent application at the German Patent and Trademark Office

• Development status: Proof of concept, ongoing research and development

  RWTH Aachen University is looking for partners for patent exploitation and/or research partners for joint development.

RWTH Technology
#00066
Fields of application
Chemical synthesis, pharmacy
Keywords
#whole-cell catalyst, #biohybrid catalyst, #chemical conversions, #organometallic compounds, #selectivity