Extensive studies have revealed that large-scale, high-cell density bioreactor cultivations have significant impact on metabolic networks of oxygen-requiring production organisms. Oxygen transfer problems associated with fluid dynamics and inefficient mixing efficiencies result in oxygen gradients, which lead to reduced performance of the bioprocess, decreased product yields, and increased production costs. These problems can be partially alleviated by improving bioreactor configuration and setting, but significant improvements have been achieved by metabolic engineering methods, especially by heterologously expressing Vitreoscilla hemoglobin (VHb). Vast numbers of studies have been accumulating during the past 20 years showing the applicability of VHb to improve growth and product yields in a variety of industrially significant prokaryotic and eukaryotic hosts. The global view on the metabolism of globin-expressing Escherichia coli cells depicts increased energy generation, higher oxygen uptake rates, and a decrease in fermentative by-product excretion. Transcriptome and metabolic flux analysis clearly demonstrate the multidimensional influence of heterologous VHb on the expression of stationary phase-specific genes and on the regulation of cellular metabolic networks. The exact biochemical mechanisms by which VHb is able to improve the oxygen-limited growth remain poorly understood. The suggested mechanisms propose either the delivery of oxygen to the respiratory chain or the detoxification of reactive nitrogen species for the protection of cytochrome activity. The expression of VHb in E. coli bioreactor cultures is likely to assist bacterial growth through providing an increase in available intracellular oxygen, although to fully understand the exact role of VHb in vivo, further analysis will be required.
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