A central problem in aerobic growth of any culture is the maintenance of di
ssolved oxygen concentration (DOC) above growth-limiting levels especially
in high-cell density fermentations that are usually of the fed-batch type F
ermenter studies have been conducted to determine the influence of DOC on t
he production of heterologous proteins in Escherichia coli. The results dem
onstrated that there is a significant degree of product-to-product variatio
n in the response of heterologous protein accumulation to DOC. For translat
ional fusions of the human immunodeficiency virus-1 (HIV-1) proteins p24Gag
and Env41, the imposition of a dissolved oxygen (DO) limitation resulted i
n 100 and 15% increases in the respective product yields. On the other hand
, the imposition of a DO limitation had no effect on the production of a si
milar translational fusion of the HIV-1 protein p55Gag, and a large negativ
e effect on the production of an influenza protein (C13). The stimulatory e
ffects of DOC on p24Gag production were investigated further. The results o
f my studies suggested that the stimulatory effect observed at reduced agit
ation rates on p24Gag accumulation was owing to an oxygen effect and not a
shear effect. Furthermore, the results of my investigations indicated that
the effect a DOC had on the production of p24Gag was strongly influenced by
the cell density at which the culture was induced.