Using enzymes as biocatalysts would provide a renewable route for the production of specialty and industrial chemicals. As the range of desired products exceeds those for which biosyntheses have been reported, this requires discovering and engineering new biosynthetic routes.

Ursula Rothlisberger and co-workers, École polytechnique fédérale de Lausanne, Switzerland, have integrated different computational methods to retrofit enzymes to synthetic pathways and generate new biosynthetic routes. Metabolic engineering methods provide a network-level analysis to deliver pathways that respect the feasible range of intracellular metabolite and enzyme concentrations, while molecular simulations assess the ability of an enzyme to catalyze a desired reaction at the atomistic scale. As a proof-of-principle, the team constructed a new reaction pathway for producing 3-hydroxypropanoate from pyruvate.

By using this combination of genome-scale modeling of the metabolic network and molecular simulations, novel reaction pathways can be assembled, modeled, and optimized in a timely manner.

• Integrating computational methods to retrofit enzymes to synthetic pathways
  E. Brunk, M. Neri, I. Tavernelli, V. Hatzimanikatis, U. Rothlisberger,
  Biotechnol. Bioeng. 2011.
  DOI: 10.1002/bit.23334