Data-based optimization of protein production processes

Biotechnol Lett. 2014 May;36(5):929-35. doi: 10.1007/s10529-013-1448-3. Epub 2014 Feb 21.

Abstract

While data-based modeling is possible in various ways, data-based optimization has not been previously described. Here we present such an optimization technique. It is based on dynamic programming principles and uses data directly from exploratory experiments where the influence of the adjustable variables u were tested at various values. Instead of formulating the performance index J as a function of time t within a cultivation process it is formulated as a function of the biomass x. The advantage of this representation is that in most biochemical production processes J(x) only depends of the vector u of the adjustable variables. This given, mathematical programming techniques allow determining the desired optimal paths u(opt)(x) from the x-derivatives of J(x). The resulting u(opt)(x) can easily be transformed back to the u(t) profiles that can then be used in an improved fermentation run. The optimization technique can easily be explained graphically. With numerical experiments the feasibility of the method is demonstrated. Then, two optimization runs for recombinant protein formations in E. coli are discussed and experimental validation results are presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors*
  • Computational Biology / methods*
  • Computer Simulation
  • Escherichia coli / chemistry
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Fermentation
  • Recombinant Proteins / biosynthesis*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Research Design
  • Solubility

Substances

  • Recombinant Proteins