Bioprocess Kinetics and Optimization of Recombinant Fermentation: Genetic and Engineering Approaches

Abstract

When a recombinant fermentation process is to be optimized and/or improved on a rational basis, many important parameters closely related to the cellular physiology and metabolism, genetic characteristics of the recombinant having foreign DNA, bioreactor environmental and operational conditions and all of their effects on productivity must be well understood and appropriate bioprocess strategy must be developed. In recombinant fermentation systems, there is a heterogeneous cell population consisting of productive plasmid-harboring cells and non-productive plasmid-free cells. Their cell population dynamics and fraction of productive cell population must be understood. Determination of key genetic parameters and assessment of their effects on the heterogeneous cell population and the productivity of genetically engineered recombinant organisms are very important to the design, control, and optimization of large- scale recombinant fermentation processes [1].

As part of our continuing endeavor to improve and/or optimize the recombinant fermentation process, the genetic and engineering approaches are considered and some highlights of our recent research results are presented in this paper. A few selected examples of bioprocess strategies which enable incremental improvements of recombinant fermentation processes include: (1) use of par sequence to improve the growth rate of the recombinant, (2) increasing translation efficiency of the recombinant by increasing the growth rate and productive cell concentration, and (3) use of optimized temperature and dilution rate control strategies.