The effect of carbon source and feeding conditions on the production of clavulanic acid (CA) and cephamycin C (CephC) by Streptomyces clavuligerus was investigated. In fed-batch experiments performed with glycerol feeding, production of CA exceeded that of CephC, and reached 1022 mg.L-1. Highest CephC production (566.5 mg.L-1) was obtained in fed-batch cultivation with glycerol feeding. In fed-batch experiments performed with starch feeding, the production of CephC was in general higher than that of CA. A dissociation index (DI) was used to identify feeding conditions that favored production of CephC relative to CA. In all cultures with glycerol, DI values were less than unity, indicating higher production of CA compared to CephC. Conversely, in cultures fed with starch, the DI values obtained were greater than unity. However, no carbon source or feeding condition was able to completely dissociate the production of CA from that of CephC.

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.

This paper reports on the use of the gas balance and dynamic methods to obtain an estimate of the volumetric oxygen transfer coefficient (kLa) in a conventional reactor during the growth phase of the microorganism Cephalosporium acremonium. A new way of calculating kLa by the dynamic method employing an electrode with a slow response, is proposed. The calculated values of kLa were used in the training of a feedforward neural network, for which the inputs were the parameter measurements of the related variables. The neural network technique proved effective, predicting values of kLa accurately from input data not used during the training phase. In contrast, the gas balance method was shown to be less useful. This could be attributed to the poor data obtained with the apparatus used to measure the oxygen in the exhaust gas, explained by the low rate of oxygen consumption by the microorganism.