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A complex medium was used to investigate the effects of shear on the S. erythraea fermentation at 7-l scale. Maximum biomass was 11.1 0.5 g l A1 at 1250 rpm (tip speed 4.45 ms A1 ), whereas it was 12.7 0.2 g l A1 at 350 rpm (tip speed 1.07 ms A1 ). Speci®c erythromycin production was not stirrer speed dependent in the range of 350 to 1000 rpm and decreased by 10% at stirrer speed of 1250 rpm. Morphological measurements using image analysis showed that the major axis of the mycelia (both freely dispersed and clumps) decreased after the end of the rapid growth phase to a relatively constant value (equilibrium size) dependent on the stirrer speed. The mechanical properties of the cell wall were examined by disruption of fermentation broth in homogeniser and it was shown that mechanical strength of the cell wall increased in a large extent during deceleration phase. IntroductionIn submerged cultures the provision of agitation to the broth is dictated by the requirement for adequate oxygen transfer rate and bulk mixing, often subjecting the ®la-mentous organisms to strong¯ow forces [1, 2, 3]. These forces may lead to physical damage, changes in morphology and variations in the rate of production of secondary metabolites [4,5,6,7]. In addition, changes in the morphology of the organism can affect the rheology of the culture [8,9,10], affecting mass transfer parameters in the fermenter [11,12] and the downstream processing such as micro®ltration.Over 60% of antibiotics of microbial origin are produced from actinomycetes ®lamentous organism, including b-lactams, polyketides, aminoglycosides and peptide antibiotics. While there are many reports for the effect of shear environment on fermentation of ®lamentous fungi in the stirred tank [4,6,7,13,14,15], there are very few quantitative studies in the case of the actinomycetes ®la-mentous organisms. Belmar-Campero and Thomas [16] studied the effect of stirrer speed in 5-l fermentation for S. clavuligerus. They found that increasing the agitation speed accelerated the fragmentation and subsequent regrowth. Martin et al. [17] reported a decrease in the mean mycelia diameter from 124 lm to 70 lm when the stirrer speed in a 3-l S. erythraea fermentation increased from 750 rpm to 1250 rpm.In the present work the effect of shear on morphology, growth and erythromycin production of S. erythraea in stirred tank bioreactor is investigated. In the majority of the reports in the literature it is impossible to distinguish the effect of mechanical shear forces from other effects such as oxygen transfer rates. In this study dissolved oxygen tension was kept above 60% of air saturation by adding oxygen to the air inlet when necessary. It has been reported that no signi®cant effects on growth, morphology, and productivity are to be expected from such a DOT level [16], therefore, differences in culture behaviour may be considered to be mainly due to mechanical forces. Materials and methods MicroorganismThe organism used was Saccharopolyspora erythraea CA340 kindly denoted by Abbott Laborat...

-Submerged cultivation of Saccharopolyspora erythraea, at different initial spore concentrations, was carried out to study the inter-relationship between inoculum concentration, morphology, rheology and erythromycin production. Pellet morphology was dominant in runs at 10 3 and 10 4 spore/ml initial spore concentrations, whereas there was a significant presence of clump morphology in runs at initial spore concentrations of 10 5 -10 7 spore/ml. The S. erythraea cultivation broths exhibited Newtonian rheology in runs at initial spore concentrations of 10 3 and 10 4 spore/ml, whereas at higher initial spore concentrations the rheological data could be fitted with the power law model. Runs in which clump morphology was predominant resulted in the highest erythromycin productivities. The findings of the present work suggest that the predominance of clump morphology, smaller sized clumps and, in the case of non-Newtonian S. erythraea cultivation broths, a decrease in viscosity enhance erythromycin production.

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T h e effect of culture conditions on the production of erythromycin by S a c c h a r o p o l y s p o r a e r y t h r a e a in batch culture SUMMARY Saccharopolyspora erythraea growth is inhibited when grown at a low constant dissolved oxygen tension (DOT) of 10% air saturation. However, the specific erythromycin production is virtually identical to that o f a culture where the DOT did not fall below 65%. In addition, at constant DOT (10%) a stirrer speed o f 750 rpm in a 7 litre causes mechanical damage to the mycelia in comparison with result at 500 rpm.

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