High-cell-density cultivation of microorganisms.

High-cell-density cultivation (HCDC) is required to improve microbial biomass and product formation substantially. An overview of HCDC is given for microorganisms including bacteria, archae and eukarya (yeasts). Problems encountered by HCDC and their possible solutions are discussed. Improvements of strains, different types of bioreactors and cultivation strategies for successful HCDC are described. Stirred-tank reactors with and without cell retention, a dialysis-membrane reactor, a gas-lift reactor and a membrane cyclone reactor used for HCDC are outlined. Recently modified traditional feeding strategies and new ones are included, in particular those for unlimited growth to very dense cultures. Emphasis is placed on robust fermentation control because of the growing industrial interest in this field. Therefore, developments in the application of multivariate statistical control, artificial neural networks, fuzzy control and knowledge-based supervision (expert systems) are summarized. Recent advances using Escherichia coli--the pioneer organism for HCDC--are outlined.