The influence of glycerol and ornithine feeding on clavulanic acid (CA) production by Streptomyces clavuligerus was investigated. In batch experiments, CA maximum concentration (Cp max) ranged randomly from 430 to 560 mg.L-1, with a maximum increase of 10% in relation to the control run, without ornithine. However, the maximum volumetric productivity of CA (Pp max) of 13.7 mg.L-1.h-1 was obtained with 0.66 g.L-1 of ornithine, 44.2% higher than the Pp max in the control run. In fed-batch experiments, Cp max varied within the narrow range from 1.254 to 1.405 g.L-1, 2.5 times higher than that obtained in the control run. The presence of ornithine increased the Pp max, although it influenced only slightly the Cp max. Concerning glycerol, the highest CA production of 1.6 g.L-1 was obtained in the fed-batch with glycerol and ornithine (180 and 3.7 g.L−1) in a 10-L bioreactor, showing a positive effect of ornithine and glycerol, in the proper proportion (48.6:1), on CA biosynthesis.

The kinetics of clavulanic acid production process by Streptomyces clavuligerus NRRL 3585 was studied. Experiments were carried out in a 4 liters bioreactor, utilizing 2 complex media containing glycerol as the carbon and energy source, and peptone or Samprosoy 90NB (soybean protein) as nitrogen source. Temperature was kept at 28°C and the dissolved oxygen was controlled automatically at 40 % saturation value. Samples were withdrawn for determination of cell mass (only peptone medium), glycerol and product concentrations. Gas analyzers allowed on line determination of CO2 and O2 contents in the exit gas. With Samprosoy, cell mass was evaluated by determining glycerol consumption and considering the cell yield, Y X/S, as being the same for both cases. Oxygen uptake and CO2 production rates were strongly related to growth and substrate consumption, allowing determination of stoichiometric constants in relation to growth, substrate, oxygen, product and carbon dioxide.

In the present work rheological characteristics and volumetric oxygen transfer coefficient (kLa) were investigated during batch cultivations of Streptomyces clavuligerus NRRL 3585 for production of clavulanic acid. The experimental rheological data could be adequately described in terms of the power law model and logistic equation. Significant changes in the rheological parameters consistency index (K) and flow behavior index (n) were observed with the fermentation evolution. Interesting correlations between the consistency index (K)/biomass concentration (C X) and the flow behavior index (n)/biomass concentration were proposed. Volumetric oxygen mass transfer coefficient (kLa) was determined by the gas balance method. Classical correlation relating the volumetric oxygen mass transfer coefficient to the operating conditions, physical and to transport properties, including apparent viscosity (muap), could be applied to the experimental results.